NUTRITIONAL CHALLENGES IN MYELOFIBROSIS PATIENTS TREATED WITH STEM CELL TRANSPLANTATION Melissa Levine Sodexo Dietetic Internship 2012-2013

TABLE OF CONTENTS Introduction........................................................................................................................

1

Discussion of the Disease................................................................................................... 2-22

I. Myelofibrosis........................................................................................................ 2-4

II. Symptoms............................................................................................................ 4-6

III. Methods of Diagnosis........................................................................................ 7-8

IV. Prognosis........................................................................................................... 8-9

V. Palliative Treatment Options.............................................................................. 9-12

VI. Curative Treatment: Stem Cell Transplantation............................................... 12-21

VII. New Treatment Options................................................................................... 21-22

Medical Nutrition Therapy............................................................................................... 23-50

I. Goals of Medical Nutrition Therapy..................................................................... 23

II. Nutrition Requirements for Adults...................................................................... 23-28

III. Nutrition Management and Support................................................................... 29-31

IV. Treatment Side Effects and Nutritional Interventions....................................... 31-38

V. GVHD and Nutritional Interventions.................................................................. 38-41

VI. Nutrition Care Process....................................................................................... 41-50

Presentation of the Patient................................................................................................ 51

Medical and Nutritional Hospital Course........................................................................ 52-57

Critical Comments............................................................................................................. 58-59

Patient Update.................................................................................................................... 60

Summary............................................................................................................................. 61

Medication Bibliography................................................................................................... 62-69

References........................................................................................................................... 70-72

Appendix............................................................................................................................. 73-78

1

INTRODUCTION My previous knowledge of the nutritional implications involved in cancer treatment was

somewhat rudimentary; I knew the basics in that it involved taste changes and weight loss, but

beyond that I was never fully aware of the nutritional struggles patients face and how they can

affect their overall chance of survival. I was also unaware of the side effects of medications that

ease symptoms but cause other unintended nutritional issues. Finally, I was unaware of the

challenges care teams face in prioritizing diagnoses and nutritional interventions when the

treatment to cure the cancer leads to other medical complications.

When my oncology rotation at Mount Sinai was approaching, I was given a variety of articles to

study before beginning. Through these articles, my interest in stem cell transplantation increased

as I was intrigued by how much of a role nutrition plays in patient care in this population. Once

my rotation started, I began to see and appreciate the interactions between the dietitian and

patients and also the dietitian and the other disciplines involved in patient care. The team

approach was especially interesting to experience, and – as I learned – patient care in this

population is often about prioritizing interventions to best meet the needs of the patient, and

therefore communication is key.

For all of these reasons and more, I chose the topic of nutritional management in patients treated

with stem cell transplantation. In entering into the research portion of this paper, I wanted to

learn as much as possible about how to manage symptoms and keep a patient nutritionally sound

in the short- and long-term post-treatment. This paper offers a thorough review of the research

available now and what we can expect in the future.

2

DISCUSSION OF THE DISEASE I. MYELOFIBROSIS

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) characterized by progressive bone

marrow fibrosis and hematopoiesis. The word myelofibrosis stems from the prefix “myelo-”

meaning “from the marrow” and “fibrosis” meaning “formation of scar tissue.” In normal

individuals, hematopoietic stem cells (immature cells) are created in the bone marrow and

gradually mature into one of two specialized cells: a myeloid stem cell or a lymphoid stem cell.

Lymphoid cells become white blood cells while myeloid cells become one of three mature cells.

These mature cells include red blood cells that carry oxygen throughout the body, white blood

cells that fight infection, and platelets that create blood clots.1

1

Individuals with an MPN have slow-growing cancer of the blood – also known as a chronic

leukemia – in which “large numbers of abnormal red blood cells, white blood cells, or platelets

grow and spread in the bone marrow and the peripheral blood”.1 In short, the bone marrow –

3

which produces the body’s cells – produces cells that develop and/or function in an abnormal

way. The six MPN’s include:

• Chronic myelogenous leukemia (CML) – hyperproliferation of abnormal white blood cells (granulocytes) in the bone marrow

• Polycythemia vera (PV) – hyperproliferation of red blood cells in the bone marrow

• Essential thrombocythemia (ET) – hyperproliferation of platelets in the bone marrow

• Chronic neutrophilic leukemia (CNL) – too many blood stem cells become neutrophils

• Chronic eosinophilic leukemia (CEL) – hyperproliferation of white blood cells (eosinophils) in the bone marrow

• Myelofibrosis (MF) – abnormal blood cells and fibers form in the bone marrow

MF is the most rare of the MPN’s and is the most difficult to diagnose due to its similarity in

symptoms to those of the other MPN’s. MF has a yearly incidence of 5-10 cases per 1 million

people (or <2 people per 100,000) with an average age of 65. As defined by the National Cancer

Institute, in primary MF “large numbers of blood stem cells become blood cells that do not

mature properly (blasts).”2 A main feature of MF is the production of too many megakaryocytes,

which are giant cells in the marrow that break up into fragments and produce hundreds to

thousands of platelets. Platelets are small blood cells that stick to the site of a blood vessel injury

and form a plug to seal off the injured vessel to stop bleeding. “Normally, new platelets are made

to replace used platelets in the body.

With MF, extra magakaryocytes are

made and many die off too early which

causes excess platelets to be released

into the blood and chemicals called

4

cytokines to be released into the marrow. The cytokines stimulate the development of collagen

and fibrous connective tissue in the marrow”.2 This fibrous tissue inside the bone marrow then

becomes increasingly thick and slows the blood-forming tissue’s ability to make blood cells.

This leads to a severe reduction in the creation of red blood cells in the bone marrow. In order to

make up for the low number of blood cells made in the bone marrow, the liver and spleen begin

to make the blood cells.1 This often leads to splenomegaly, a major characteristic of MF, and less

commonly leads to hepatomegaly.

There are two types of MF, which are characterized mainly by the disease course. The first is

primary myelobibrosis (PMF), which presents as a “de novo” disorder, and the second is

secondary MF, which evolves from polycthemia vera (post-PV MF) or essential

thrombocythaemia (post-ET MF).4 Both types of MF are MPN’s and are characterized by bone

marrow fibrosis, osteosclerosis, extramedullary hematopoiesis (EMH), splenomegaly, abnormal

cytokine expression, and leucoerythroblastic anemia”.3,4

II. SYMPTOMS

The main characteristics of MF are collagen fibrosis in the bone marrow leading to anemia,

leucopenia (low WBCs) or leukocytosis (high WBCs), thrombocytopenia (low platelets), and

extramedullary haemopoiesis (blood formed outside of the bone marrow) leading to

splenomegaly.4 Constitutional symptoms of MF often arise from splenomegaly and include

pain/fullness below the ribs on the left side, early satiety, fatigue, dyspnea, bruising easily, fever,

night sweats, pruritus, and weight loss.1

A. Collagen fibrosis

“Clonal myeloproliferation in MF is accompanied by bone marrow fibrosis, from which

the name of MF is derived historically. Although fibrosis is recognized as a secondary

5

phenomenon, it remains pathognomonic for MF. In the prefibrotic stage, the bone

marrow displays marked hypercellularity with several classes of atypical megakaryocytes

and granulocytes, followed by reticulin collagen fibrosis or osteosclerosis in the fibrotic

stage. The fibrotic stage is typically associated with leukoblastosis, hepatic

splenomegaly, and extramedullary hematopoiesis (EMH), particularly in the spleen but

also at other sites. Cellular abnormalities in MF are detected in a peripheral blood smear,

which typically shows nucleated red blood cells and immature granulocytes. The

development of reticulin and/or collagen fibrosis in the bone marrow space in MF

contributes to insufficient hematopoiesis followed by worsening cytopenias, resulting in

significant morbidity and mortality”.5

B. Anemia, leucopenia, thrombocytopenia

Anemia, leucopenia, and thrombocytopenia are caused by the basic feature of MF: blood

cells are produced in the bone marrow and do not mature. In MF patients, “one blood

stem cell acquires the ability to reproduce without regulation, producing large numbers of

immature blood cells”.5 These cells look like tear-drop shaped red cells and do not

function properly. “The body continues to produce these abnormal, non-functional cells,

leaving little space for healthy cells. At the same time, these cells release chemicals that

cause the bone marrow to become fibrous or fill with scar tissue, further interfering with

the ability to produce healthy blood cells. In addition, these abnormal cells may be

produced in other areas of the body, most often the spleen or liver, which results in an

enlarged spleen or liver that can be felt by the physician”.5 In MF, too few red blood cells

are made due to the fibrosis, whereas too many white blood cells and platelets form.

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C. Extramedullary Hematopoiesis and Splenomegaly

Extramedullary hematopoiesis is a result of the bone marrow’s inability to produce new

blood cells once the fibrous tissue forms within the bone. It has also been shown that MF

causes the bone marrow to leak, and cells are released into the blood that are normally

not in the blood. These cells tend to gravitate towards the spleen where they take up

residence and begin hematopoiesis. This gradually causes the spleen to become enlarged,

which is a key characteristic of MF. “Splenomegaly, resulting from extramedullary

hematopoiesis, accounts for some of the most debilitating symptoms of MF, whether

primary or secondary to PV or ET. It contributes to the morbidity associated with MF by

causing early satiety, dysregulated gastrointestinal function, portal hypertension,

decreased physical activity, distressing abdominal pain, and worsening of assorted

cytopenias secondary to splenic sequestration. About 10% of MF patients present with

severely symptomatic splenomegaly at diagnosis; another 50 % will develop it within 4

years”.6

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III. METHODS OF DIAGNOSIS

Many of these characteristics and symptoms are used to diagnose MF. However, due to the rarity

of MPN’s and the similarities between them, there have been difficulties over the years in setting

specific diagnostic criteria. The World Health Organization (WHO) has well-established

diagnosis criteria, which is detailed in Table I.7 A more basic approach which is used more often

in practice is describe in Table II.4

TABLE I. The 2008 World Health Organization (WHO) diagnostic criteria for primary myelofibrosis Diagnosis requires meeting all three major criteria and two minor criteria. Major criteria 1. Presence of megakaryocyte proliferation and atypia,* usually accompanied by reticulin and/or collagen fibrosis, or in the absence of significant reticulin fibrosis, the megakaryocyte changes must be accompanied by an increased bone marrow cellularity characterized by granulocytic proliferation and often decreased erythropoiesis (ie, prefibrotic cellular-phase disease) 2. Not meeting WHO criteria for polycythemia vera,† BCR-ABL1+ chronic myelogenous leukemia,‡ myelodys- plastic syndrome,§ or other myeloid neoplasms 3. Demonstration of JAK2V617F or other clonal marker (eg, MPLW515L/K), or in the absence of a clonal marker, no evidence that the bone marrow fibrosis or other changes are secondary to infection, autoimmune disorder, or other chronic inflammatory condition; hairy cell leukemia or other lymphoid neoplasm; metastatic malignancy; or toxic (chronic) myelopathies.¶ Minor criteria 1. Leukoerythroblastosis** 2. Increase in serum lactate dehydrogenase level** 3. Anemia** 4. Splenomegaly** *Small to large megakaryocytes with an aberrant nuclear/cyto- plasmic ratio and hyperchromatic, bulbous, or irregularly folded nuclei and dense clustering. †Requires the failure of iron replacement therapy to increase hemoglobin level to the polycythemia vera range in the presence of decreased serum ferritin. Exclusion of polycythemia vera is based on hemoglobin and hematocrit levels; red cell mass measurement is not required. ‡Requires the absence of BCR-ABL1. §Requires absence of dyserythropoiesis and dysgranulopoiesis. ¶Patients with conditions associated with reactive myelofibrosis are not immune to primary myelofibrosis, and the diagnosis should be considered in such cases if other criteria are met. **Degree of abnormality could be borderline or marked. TABLE II. Diagnostic criteria for MF: diagnosis requires A1 + A2 and any two B criteria4 A1 Bone marrow fibrosis ! 3 (on 0–4 scale) A2 Pathogenetic mutation (e.g. in JAK2 or MPL), or absence of both BCR-ABL1 and reactive causes of bone

marrow fibrosis B1 Palpable splenomegaly B2 Unexplained anemia B3 Leuco-erthroblastosis B4 Tear-drop red cells B5 Constitutional symptoms* B6 Histological evidence of extramedullary haematopoiesis *Drenching night sweats, weight loss >10% over 6 months, unexplained fever (>37·5°C) or diffuse bone pains.

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A. Gene Mutations – JAK2

JAK2V617F is noted in the diagnostic criteria above. The presence of a JAK2 mutation is

found in approximately 45-68% of patients diagnosed with MF and should therefore be

screened using a molecular genetic assay during the diagnostic process.9 “The gene

mutation causes abnormal signaling in the JAK pathway, which regulates blood cell

production”.2

IV. PROGNOSIS

Prognosis in MF is important, especially in determining the course of medical action to take with

each individual patient. With options ranging from managing symptoms to chemotherapy and/or

stem cell transplantation, an accurate assessment of a patient’s prognosis is critical. Prior to

2009, the Lille Score model was used to assess prognosis. In 2009, Cerantes et al published the

International Prognostic Scoring System (IPSS), which uses five risk factors to estimate survival

from the time of diagnosis (see Table III below).4 In 2010, Passamonti et al modified the scoring

system to include a feature to make it dynamic, aptly called the Dynamic IPSS in which risk

factors are assessed throughout their disease, not just at diagnosis. There is a further modification

called the DIPSS Plus which shows additional risk factors for platelet count of < 100 x 109/l,

RBC transfusion dependence, and unfavorable karyotype.4 Studies have shown that those with

unfavorable an karyotype are at high risk of leukemic transformation.10

TABLE III. PROGNOSTIC CRITERA4 Variable IPSS DIPSS

Age >65 years " " Constitutional symptoms " " Hemoglobin <100 g/l " " Leukocyte count > 25 x 109/l " " Circulating blasts ! 1% " " DIPSS-Plus: add 1 point to the DIPSS RISK GROUP* (low = 0; intermediate 1 = 1, intermediate 2 = 2 and high risk = 3) in addition for: Platelet count <100 x 109/l , RBC transfusion need, Unfavorable karyotype

9

IPSS DIPSS DIPSS-Plus Risk Group Predictors (n) Median

Survival (yrs) Predictors (n) Median

Survival (yrs) Predictors (n) Median

Survival (yrs) Low 0 11.3 0 Not reached 0 15.4 Intermediate-1 1 7.9 1 or 2 14.2 1 6.5 Intermediate-2 2 4 3 or 4 4 2-3 2.9 High !3 2.3 5 or 6 1.5 !4 1.3 *Note that this is the risk group NOT the sum of points.

V. PALLIATIVE TREATMENT OPTIONS

Pharmaceutical MF treatment aims to relieve symptoms and reduce the risk of complications and

therefore is only considered palliative and often short-lived. As noted above, some of the main

characteristics of MF are splenomegaly from extramedullary haemopoiesis and anemia, along

with a variety of other constitutional symptoms including pain/fullness below the ribs on the left

side, early satiety, fatigue, dyspnea, fever, night sweats, pruritus, weight loss and increased risk

of infection. The only potential cure for MF is allogeneic stem cell transplantation (ASCT).

Below is a review of the palliative treatment options for the most common symptoms of MF:

A. Splenomegaly

1. Hydroxycarbamide/Hydroxyurea (HU)

HU, an oral chemotherapeutic myelosuppressive agent, is the most commonly

used drug therapy to treat an enlarged spleen, although clinical support is limited

to a few studies showing its efficacy.4 Regardless, it remains widely used and is

often the first line of therapy when patients are diagnosed with MF, specifically

because diagnosis normally presents with an enlarged spleen. The spleen becomes

enlarged in MF patients because hematopoiesis takes place there when the bone

marrow fails to produce enough blood cells. Splenomegaly is often targeted first

to treat because it causes the most constitutional symptoms such as early satiety

and weight loss. However, “the primary side-effect of hydroxyurea is suppression

10

of blood counts, particularly the white blood cells (neutropenia) and platelets

(thrombocytopenia). Neutropenia and thrombocytopenia respectively place

patients at risk for infection and bleeding”.11 Therefore, the patient’s degree of

cytopenia is considered when administering HU.

2. Bulsulfan and Melphalan

Bulsulfan and melphalan are cancer-fighting alkylating agents and are often used

in low doses in patients when HU is no longer indicated due to cytopenia.

Alkylating agents “work by reacting with the proteins that bond together to form

the very delicate double helix structure of a DNA molecule, adding an alkyl group

to some or all of them. This prevents the proteins from linking up as they should,

causing breakage of the DNA strands and, eventually, the death of the cancer cell.

This phenomenon is essentially a mutation that takes away the cancer cell’s

ability to multiply”.12 With the low dose administration, the disease slows and

more normal blood cells can be produced in the bone marrow, therefore helping to

reduce the size of the spleen.

3. Splenectomy

Removal of the spleen is rarely indicated but is done if drug therapies do not

work, leaving the spleen extremely enlarged or causing severe anemia, low

platelet count or portal hypertension. Splenctomies have not proven to rid the

body of the disease state and can cause a variety of other complications.

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B. Cytopenia

1. Interferon (IFN)-! and PEG-IFN !

“The interferons are a group of natural proteins that are produced by human cells

in response to viral infection and other stimuli. They were first described in 1957,

and were named for their ability to interfere with viruses that are replicating”.13

Initially, INF-! was used due to its cytoreductive properties. It has been shown to

“reverse cytopenias and bone marrow abnormalities in patients with earlier forms

of MF, prior to the advent of extensive fibrosis”.5 However, due to the

inconvenient dosing schedule and increased risk of toxicity, its use is limited.

However, a study published in 2009 showed the efficacy of pegylated (PEG) INF-

! in achieving hematologic responses and placing the majority of patients in

remission or experiencing major positive responses.14 To date, this is the only

study using PEG INF-! in treatment for MF, however interest is growing in this

area.5

C. Anemia

As described above, MF results in the proliferation of too few red blood cells and an

overabundance of white blood cells and blood platelets, therefore causing severe anemia.

Treatments for anemia aim to either replenish the red blood cells and/or reduce the

symptoms of anemia, such as fatigue and weakness.

1. Red blood cell transfusions

MF patients often experience anemia, either through lack of hematopoiesis in the

bone marrow due to fibrosis, ineffective production of RBC in extramedullary

sites (i.e. the spleen), or from pharmaceutical drugs such as HU that reduce the

12

extramedullary hematopoiesis, among other factors. However, this can often

result in iron overload, which requires iron-chelating agents. The iron-chelating

agents help prevent organ damage from the iron-overload and have been proven

to “significantly improve the overall survival of red blood cell transfusion–

dependent PMF patients.”5

2. Erythropoietin and Androgen Therapy

Erythropoietin is a hormone that stimulates the production of red blood cells in

the bone marrow. In states of chronic inflammation, such as cancer, serum

erythropoietin (EPO) levels in the blood can get very low and therefore cause

anemia. Recombinant human erythropoietin (rHuEPO) provides an alternative to

blood transfusions and is often used to improve red blood cells levels. Danazol, an

androgenic steroid, is another drug used to treat anemia and/or relieve the

symptoms of severe anemia. This treatment has approximately a 33% success

rate, may cause masculinizing effects in women and can cause liver damage;

therefore, this is not a first line therapy for patients.2

VI. CURATIVE TREATMENT: STEM CELL TRANSPLANTATION

Stem cell transplantation (SCT) has proven to be the only curative therapy for MF patients. The

main goal of SCT is to replace the damaged bone marrow and diseased cells with healthy cells in

order to restore normal hematopoietic and immunologic function.15 While there are three types of

STC, listed below, the only options for MF patients is allogeneic.

A. Autologous SCT (Auto-SCT)

In this transplant, the transplant recipient and donor is the same person. Healthy stem

cells are taken from the patient before the cancer reaches that area. Those cells are then

13

harvested and implanted later when the procedure is indicated. This type of transplant

carries a much lower risk of rejection; however, it does carry some risk involving the

potential to reinfuse the diseased cells and therefore causing a relapse.16 Another

disadvantage is that auto-STC lacks the graft versus cancer effect.

a. The graft versus cancer/tumor effect takes place in allo-STC patients. When

the donor’s healthy cells become established in the recipient’s body, the donor’s

cells may begin to recognize the recipient’s cells as foreign and therefore destroy

them. This can help destroy leftover or new cancerous cells.

B. Syngeneic SCT

Syngeneic SCT is when the recipient receives stem cells from an identical twin. This

carries the same risks an autologous SCT carries in that the immune system between the

donor and recipient are so similar that the transplant will not help to destroy anything.

Therefore, effort is made to destroy as many cancer cells as possibly before the

transplant.

C. Allogeneic (Allo-SCT)

This type of transplant involves transferring stem cells from a donor to the recipient. The

ideal donor is a human leukocyte antigen (HLA)-genotypic match from a sibling, a

match identified through the National Marrow Donor Program (NMDP).16 The four

types of stem cell transplantation considered allogeneic are:

a. HLA-matched relative (most often a sibling)

b. HLA-matched unrelated donor

c. HLA miss-matched family member

d. Unrelated umbilical cord blood

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The main advantage is that the donor cells can create an anticancer environment and

infuse disease-free cells into the host; therefore there is a greater chance for the graft

versus cancer effect. The main disadvantage is that the recipient has a much higher risk of

getting graft versus host disease (GVHD), along with prolonged immunosuppression and

the risk that it carries, including increased susceptibility to infection and graft rejection.16

a. GVHD, in short, is a condition that can happen after allo-SCT when the donor’s

cells see the recipient’s cells as foreign. This can be good, as described above in

the graft versus cancer effect, however in GVHD the donor’s cells also attack

healthy cells. This most often occurs in the skin, GI tract and liver. See below for

more information on GVHD.

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D. Sources of Stem Cells

1. Bone marrow

Bone marrow is the spongy tissue in the center of bones that creates the cells that

circulate throughout our body.31 Cells are harvested from the pelvic bone, and then

the cells are filtered, stored, and then frozen. Bone marrow stems cells were the

first stem cells ever used in practice.

2. Peripheral blood

Stem cells are taken from the blood in this case. Normally, there are few stem

cells found in the peripheral blood since they develop in the bone marrow.31

However, donors are given a “hormone-like substances called growth factors”

prior to the harvest day.31 This helps more stem cells grow and move from the

marrow to the blood. A special machine is used to collect the peripheral blood and

then separate the stem cells out so that the rest of the blood goes back to the

donor. “Since 1994, peripheral stem cells have been the most frequent source of

cells used for transplant. They are associated with accelerated engraftment and

result in reduced length of hospitalization.”16

3. Umbilical cord blood

“Around 30% of unrelated hematopoietic stem cell transplants are done with cord

blood.”31 The umbilical cord is taken after a baby is born and stored for later use.

The cord can be from the recipient him/herself or a donor. “Stem cells collected

from umbilical cord blood have the advantage of being immunological immature

and can therefore be used with broader HLA disparity, but the quantity of stem

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cells from umbilical cord blood is often too low for adults and these transplants

have been associated with delayed engraftment.”16

E. Patient Selection

HSTC is not indicated for everyone with MF due to the high risk of morbidity and

mortality in SCT patients, therefore the prognostic scoring systems are essential when

deciding whether a patient should go through with the procedure. With that noted, MF is

increasingly being treated with allo-SCT as shown in the trends generated by Center for

International Blood and Marrow Transplant Research.18 With advances in SCT and the

fact that it is the only curative option, patients and doctors seem to be turning to it more

and more.

F. Course of Therapy

In allo-SCT, patients first receive high doses of chemotherapy called myeloablative

therapy and/or radiation therapy in order to destroy the diseased bone marrow.2 The high

dose chemotherapy normally takes place for about five to seven days. After a day of rest,

healthy hematopoietic stem cells from a donor are infused into the MF patients. The

donor is someone whose stem cells are compatible with those of the patient, who is often

a sibling who is a match but can be someone unrelated as well. The new cells are

supposed to grow and multiply in the bone marrow, creating a healthy number of red

cells, white cells and platelets.2 There is also new research in reduced intensity SCT that

is being tested in an effort to lower treatment-related mortality (TRM).4

G. Side Effects of Conditioning

Medications for chemotherapy and the effects of radiation can be harsh on one’s body.

See the “Medication Bibliography” for a list of medications, their uses, mechanisms of

17

action and nutritional side effects. Below are the major effects chemotherapy and

radiation can have on the body during treatment.

a. Gastrointestinal Tract – Common problems include mouth sores, nausea,

diarrhea, cramps, nausea and vomiting.

b. Hair – Hair loss can occur during treatment and is usually temporary.

c. Heart – Depending on a variety of factors, including current health status, the

heart can be affected by treatment. Tests prior to transplant are often

conducted to check the strength of the heart.

d. Lungs – A tissue reaction within the lungs to treatment can cause interstitial

pneumonitis pneumonia. This can be very severe and prevent the efficient

exchange of oxygen in the lungs.

e. Skin – Severe rashes may develop.

f. Blood Vessels – Leaky blood vessels may develop and cause fluid

accumulation in the lungs, leading to congestion, poor oxygen exchange and

shortness of breath.

g. Liver – Sinusoidal obstructive syndrome (SOS) may occur due to blocked

blood vessels in the liver, which may result in liver damage and accumulation

of fluid in the abdomen.

h. Immunosuppression – The conditioning treatment causes a suppressed

immune system due to cells (both healthy and not) killed during therapy. This,

in turn, causes a low WBC count and therefore the result is

immunosuppression.

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H. Nutritional Side Effects of Allo-SCT

1. Oral Muscositis and Esophagitis

These are a form of GVHD and therefore occur due to the new healthy cells

attacking healthy epithelial cells within the patient’s body. Cracked lips and ulcer-

like mouth sores form and lead to inflammation of the epithelial tissue within the

mouth and esophagus. This can be extremely painful and result in an inability to

consume any energy by mouth. Intravenous (IV) opioids are often needed for pain

management. Symptoms may occur within days of receiving chemo or radiation.

Healing often takes place once marrow engraftment occurs and absolute

neutrophils reach >500cm3.15

2. Xerostomia and Dysgeusia

Altered salivation in which saliva becomes thick can be due to conditioning

treatments but is also associated with drugs such as antiemetics, antidepressants,

and opiate-containing pain medications.15 Impaired taste (or sometimes

diminished taste) are also effects of conditioning treatments and medications such

as morphine and antibiotics. Xerostomia often leads to dysgeusia. These changes

are normally temporary.15 These also lead to low energy intake throughout

treatment.

3. Nausea and Vomiting (N/V)

These are caused by a large variety of factors, including conditioning treatments,

medications, GI infections, intestinal GVHD, and fluid/electrolyte imbalances.15

Antiemetics are the first course of treatment for N/V and have variable success

depending on the cause and the patient’s tolerance. Both symptoms lead to

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nutritional deficiencies, as appetite decreases when this occurs and nutrients taken

in are not absorbed properly.

4. Anorexia

Anorexia throughout treatment is caused by all of the factors listed above (mouth

pain, altered taste, N/V, electrolyte imbalances, medications) along with early

satiety from delayed gastric emptying and loss of appetite, GI infections,

intestinal GVHD, and general discomfort from treatment.15

5. Diarrhea and Steatorrhea

Diarrhea is associated with all of the symptoms listed above, along with lactose

intolerance, laxatives, and supplemented magnesium salts.15 Steatorrhea and fat

malabsorption may develop from liver and GI GVHD.15

6. Sinusoidal obstructive syndrome (SOS)

SOS is a common side effect of high dose chemotherapy and radiation; however,

its pathogenesis is not completely understood as its incidence has been

documented to occur in less than 5% of patients to more than 70% depending on

the population studied and the difference in conditioning therapy used prior to

transplant.21 It is understood to cause hepatic vein obstruction due to

subendothelial edema and fibrin deposits, which prevents blood from flowing out

of the liver and back to the heart, which then leads to liver toxicity and damage.20

Basically, liver dysfunction occurs due to blocked blood vessels through the liver,

which may result in liver damage and accumulation of fluid in the abdomen.11

Clinical symptoms include weight gain with ascites, increased serum bilirubin and

jaundice, and hepatomegaly, all of which can lead to hepatorenal failure and

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encephalopathy. Those with a history of liver disease (hepatitis C, hepatc fibrosis,

cirrhosis) and second transplants are at a higher risk of developing this.15,20

7. Renal Complications

There are a variety of factors that may lead to renal complications from SCT

treatment. The most common include side effects of chemotherapy, radiation, and

medications during these treatments and post-SCT, including cyclosporine,

tacrolimus, amphotericin, aminoglycosides, bancomycin, and trimethoprim-

sulfamethoxazole are associated with renal damage. Other causes include

radiocontrast agents, extreme dehydration, and hepatorenal syndrome.

8. Infection

Infections throughout cancer treatment are common due to treatment causing

immunosuppression. Patients are at an increased risk for viral, bacterial, and

fungal infections. One study that measured the long-term survival of patients post-

allo-SCT found that serious infections are the third leading cause of death. More

specifically, it found that it accounts for 4-20% of deaths beyond two years post-

transplant. To evaluate immunocompetence, the following calculation can be done

to determine the total lymphocyte count (TLC)19: TLC = (WBC x %lymphocytes)

/ 100

G. Graft Versus Host Disease (GVDH)

“Graft-versus-host disease (GVHD) is a complication that can occur after a stem cell or

bone marrow transplant in which the newly transplanted donor cells attack the transplant

recipient's body.”33 GVHD only occurs in allo-SCT. GVHD can develop in the

oral/mouth area, skin, GI tract or liver (these are described in detail in the Medical

21

Nutrition Therapy section below). Depending on when the GVHD develops, it can be

categorized as acute or chronic:

1. Acute GVHD

This occurs within 100 days post-transplant in 40-50% of patients and usually

affects the skin, liver and GI tract. See the “Medications Bibliography” section at

the end of this paper. Medications to help with symptoms include topical steroids,

antiemetics, pain medications, fluid and electrolyte replacement, and

antiidiarrheals.16 See Table XIV for staging parameters of acute GVHD. This can

be helpful for the medical team to determine a patient’s disease state and course

of action prior to performing a biopsy.

2. Chronic GVDH

This occurs beyond 100 days post-transplant in 40-70% of patients and can affect

the skin, liver, GI tract, eyes, musculoskeletal, nervous, hematopoietic, and

pulmonary symptoms. Medications for this are listed in the “Medications

Bibliography” section, as well.

VII. NEW TREATMENT OPTIONS

As described above, the majority of patients with MF are positive for the JAK2 gene mutation,

which has led to a large amount of research into the use of JAK2 inhibitors for the treatment of

MF.5 Ruxolitinib (Jakafi) is “the first JAK inhibitor and currently the only drug approved by the

FDA to treat symptoms and signs of MF; including an enlarged spleen, night sweats, itching and

bone or muscle pain. It is indicated for treatment of patients with intermediate- or high-risk

MF”.2 Side effects include thrombocytopenia and anemia. While there is much excitement

22

surrounding Jakafi, there are few studies that prove its effectiveness. As such, it is still

considered an experimental drug in most practices.

23

MEDICAL NUTRITION THERAPY I. GOALS OF MEDICAL NUTRITION THERAPY

The main goal of medical nutrition therapy for patients receiving stem cell transplantation is

weight maintenance. Weight is a significant indicator of nutritional status in this patient

population, as it can show how well a patient is tolerating treatment or whether his/her disease

state is worsening. Since most treatments cause a variety of factors that lead to the combination

of increased needs and inadequate intake (both orally and through nutrition support as described

below), weight is extremely important to monitor and treat. In addition to weight, it is important

to educate patients on the importance of nutrition therapy throughout their treatment. Patients

may be put on a variety of diets depending on their symptoms, and it is important for the patient

and his/her family to understand the significance behind the treatment in order to remain

compliant. This specifically applies when patients are in a neutropenic state and need to follow a

low bacteria diet. Adequate protein intake and maintenance of nutrition-related labs including

electrolyte balances are important to monitor and treat, as shifts may be seen throughout

treatment due to certain medications.

II. NUTRITION REQUIREMENTS FOR ADULTS

A. Energy

Due to the individuality of treatment courses, patient response, pre-transplant nutritional

status, post-transplant symptoms and other health-related conditions, there are not set

guidelines on energy requirements for cancer patients or hematopoietic transplant

patients.22 Despite the lack of evidenced-based guidelines, it is well recorded that energy

requirements are increased in patients who receive SCT. The requirements vary due to a

variety of reasons including the length/strength of the conditioning treatments, potential

24

infections/fever, and development of GVHD causing metabolic shifts, along with with

common symptoms that cause a decrease or inadequate energy intake (including nausea,

vomiting, diarrhea, early satiety, etc…). Studies over the past thirty years have shown that

requirements can range anywhere from 30-50 kcals/kg/day throughout the course of

treatment and are generally calculated using one of the following categories:19

• Obese patients: 21-25 kcals/kg • Non-ambulatory or sedentary adults: 25-20 kcals/kg • Slightly hypermetabolic patients or those who need to gain weight, or are

anabolic: 30-35 kcals/kg • Hypermetabolic or severely stressed patients or those with malabsorption: 35

kcals/kg or greater as needed • Basal Energy Expenditure* (BEE) x activity/injury factor (1.5-2)

*BEE is calculated using the Harris-Benedict formula: • BEE Men = 66.5 + (13.75 x kg) + (5.003 x cm) - (6.775 x age) • BEE Women = 655.1 + (9.563 x kg) + (1.850 x cm) - (4.676 x age)

o The factor of 1.5-2 takes into account both the activity factor an injury factor

The most commonly used calorie goal is 30-35 kcals/kg/day with higher energy

requirements reserved for only the most severe cases of malnourishment and

hypermetabolic activity during GVHD.23 Once metabolic complications are resolved,

energy needs decrease back to a patient’s regular intake, likely 25-30 kcals/kg/day. Due

to the daily changes in metabolism and energy needs in cancer patients, a metabolic cart

is not normally indicated. The main goal of nutrition is to ensure adequate intake during a

time when intake can be compromised for a variety of reasons.

B. Protein

Protein is needed to provide tissue repair after conditioning therapy (especially radiation)

and to avoid loss of lean body mass.15 Requirements for adults after SCT are generally

1.2-1.5 g/kg/day depending on age, constitutional symptoms, energy intake, weight,

height and muscle mass. However, many studies have noted that protein requirements can

25

reach 2 g/kg/day or more during specific treatment periods (chemo/radiation, high dose

corticosteroid treatment) or due to progressive GVHD.15, 24 Protein can help to repair

tissue damage from conditioning treatments, promote tissue and cell growth (white and

red blood cells and platelets), and help to meet increased demands caused by infection,

wound healing and hypermetabolism.23 Protein may need to be further modified if

hepatic, renal, or neurologic function is altered.

1. Glutamine

Glutamine is a non-essential amino acid that has been studied in recent years for

use on SCT patients due to its proven ability to help gut function, repair tissue

damage, improve immune response, and assist in other essential body processes,

especially in times of stress. Glutamine “administration after BMT was indeed

shown to exert positive effects on nitrogen balance, incidence of infectious

complications, survival, duration of hospital stay, and need for TPN, although not

univocally.”22 Nitrogen is necessary to keep organs functioning and repair

wounds during times of injury. Glutamine provides one-third of this nitrogen.

Additionally, glutamine has proven to help prevent and/or treat SOS by

preserving hepatic function and protecting hepatocytes from oxidative stress

during treatment.22 More studies need to be conducted on this therapeutic role of

glutamine.

C. Fats

In healthy individuals, typical intake is 15-30% of daily energy.15 The recommendations

for patients with cancer and/or undergoing STC should not exceed 60% of calories due to

potential for hypercholesterolemia or hypertriglyceridemia. If high triglycerides are

26

apparent, lipid intake should not exceed 40% of total energy. “Lipids may be particularly

useful in achieving the energy target if hyperglycemia develops as a consequence of

steroid treatment or infection.”22 However, the minimum intake should not fall below 4-

8% in order to prevent essential fatty acid deficiency.15 The essential fatty acids, linoleic

(omega-6) and linolenic (omega-3), are necessary for the endogenous synthesis of other

fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA),

which are needed for healthy skin, immune system, and neurologic function.

D. Carbohydrates

There are no specific carbohydrate recommendations for cancer patients eating a diet

orally or when receiving enteral nutrition. Carbohydrates in general should be around 50-

60% of total intake. If parenteral nutrition is involved, the infusion rate recommendation

should not exceed 5 mg/kg/min. Hyperglycemia, often brought on by steroid use in

cancer patients, may deem it necessary to restrict carbohydrates or plan for consistent

intake. In cases where hyperglycemia persists, it may be necessary to increase protein and

lipid calories in order to make up for the prescribed lower carbohydrate intake.

E. Fluids

Fluid needs are dependent upon a variety of factors in cancer patients and may change

throughout the course of treatment. For adults, the standard recommendation is that fluid

intake should exceed 1500 mL/day (generally 25-30 mL/kg). When a patient is

experiencing fever, excessive GI losses, hypermetabolism, dehydration and during SCT

conditioning, fluid needs are increased. Fluid restrictions may be necessary if a patient is

experiencing edema or ascites. Intake/output should be documented daily for patients

27

with BMT, especially when symptoms involving fluid loss such as fever, emesis or

diarrhea are present. Fluid needs will increase significantly in each of these conditions.

F. Vitamins and Minerals

According to A.S.P.E.N Nutrition Support Practice Manual 2nd Edition, there are no

specific vitamin and mineral requirements for SCT patients.15 It notes, however, that

patients should receive micronutrient supplementation in order to receive 100% of the

dietary reference intakes for age throughout the first year post-transplant and/or as long

as immunosuppressive medications are given. Iron is specifically not recommended due

to the frequency of blood transfusions throughout the recovery period, as iron overload

can occur. A.S.P.E.N provides the following guidelines for patients undergoing

cytoreductive therapy and/or SCT:

1. Vitamin C

Vitamin C when used in parenteral nutrition helps to “promote tissue recovery via

collagen biosynthesis after cytoreductive therapy.”15 For most adults, the

recommendation is an additional 500 mg of vitamin C per day. Vitamin C is

contraindicated in patients with serum ferritin levels > 100 mcg/L as it can cause

oxidative damage with the free iron. In addition, it should not be used in patients

receiving hemodialysis.15

2. Vitamin K

Vitamin K deficiency may be seen in patients with malabsorptive disorders and

should be supplemented in adults with an additional 10 mg/week.15

28

3. Zinc

Zinc is a necessary supplement in patients who experience excessive diarrhea.

A.S.P.E.N. notes that when stool volume exceeds 500mL in patients 20-40 kg and

1000mL in patients >40 kg, zinc should be supplemented at 1 mg/100 mL stool.

4. Electrolytes

Electrolytes are especially important to monitor due to medication administration

and changes in GI losses. The following is a chart adapted from the A.S.P.E.N.

guidelines on the causes of hyper- and hypo- electrolyte levels:15

Electrolyte Cause of Imbalance Hypomagnesemia: diarrhea, steatorrhea, malasbsorption syndromes, medications (amphotericin, cyclosporine; foscarnet; tacrolimus), refeeding syndrome, severe malnutrition

Magnesium

Hypermagnesemia: discontinuation of magnesium-wasting medication, excessive supplementation, renal insufficiency Hypokalemia: GI losses, medications (amphotericin; corticosteroids; furosemide; foscarnet), refeeding syndrome, anabolism

Potassium

Hyperkalemia: excessive supplementation, potassium-sparing diuretics, renal insufficiency, tacrolimus Hyponatremia: excessive GI losses, fluid retention, excessive IV or oral fluid/free water intake, hyperglycemia, medications (cyclophosphamide; cyclosporine; furosemide)

Sodium

Hypernatremia: inadequate fluid replacement during GI losses, aggressive diuretic therapy, fever Hypophosphatemia: diabetes, medications (corticosteroids; cyclophosphamide; foscarnet; sirolimus), refeeding syndrome, renal acidosis, steatorrhea

Phosphorus

Hyperphosphatemia: excessive phosphorus intake, multiple myeloma, myelogenous leukemia, renal failure Hypocalcemia: medications (corticosteroids; foscarnet; pamidronate), vitamin D deficiency

Calcium

Hypercalcemia: lymphoma, metastatic breast cancer, multiple myeloma, renal failure

29

III. NUTRITION MANAGEMENT AND SUPPORT

A. Oral Feedings

Oral feedings are the preferred form of nutrition management and support. Patients

should continue consumption by mouth as long as their GI tract is functioning and they

are well nourished. In general, energy dense foods (i.e. high calorie, high protein) are

recommended, as early satiety can often be a conditional symptom of the conditioning

treatment, SCT, or the cancer itself. Other restrictions and changes may be necessary

depending on the conditional symptoms associated with the patients’ disease or treatment

state. These restrictions are discussed in the next section under “Symptom Management.”

B. Enteral and Parenteral Nutrition

Nutrition support through EN and PN is often indicated in the SCT population due to the

conditional symptoms reviewed in the next section that make it difficult for a patient to

maintain a good nutritional status. A.S.P.E.N. states the following in regard to nutrition

support therapy in SCT patients:25

1. “Nutrition support therapy is appropriate in patients undergoing hematopoietic

cell transplantation who are malnourished and who are anticipated to be unable to

ingest and/or absorb adequate nutrients for a prolonged period of time. When

parenteral nutrition is used, it should be discontinued as soon as toxicities have

resolved after stem cell engraftment. Enteral nutrition should be used in patients

with a functioning GI tract in whom oral intake is inadequate to meet nutrition

requirements.”

2. “Nutrition support therapy is appropriate for patients undergoing hematopoietic

cell transplantation who develop moderate to severe graft-vs-host disease

30

accompanied by poor oral intake and/or significant malabsorption.” The following

table reviews the indications for PN and EN in patients post-SCT.

Table IV. Indications for nutrition support in patients post-SCT Enteral Nutrition Support Parenteral Nutrition Support

• Functioning GI tract + inadequate oral intake x1 week or more

• Functioning GI tract + presence of oral/esophageal GVHD + inadequate oral intake

• Stable chronic GI GVHD + inadequate oral intake

• PN is contraindicated due to fluid retention and/or organ failure + functioning GI tract

• Central IV access not possible + enteral access possible + functioning GI tract

• Failure to thrive + functioning GI tract

• Presence of mucositis and or esophagitis during early post-transplant phase

• Intractable vomiting or diarrhea (>500 mL) from acute GI GVHD requiring bowel rest

• Severe thrombocytopenia prohibiting enteral access

• History of nonhealing wounds or extensive chronic skin GVHD preventing permanent enteral access

• Fail to receive adequate nutrition via enteral route

Table adapted from Graft-vs-Host Disease: Nutrition Therapy in a Challenging Condition23 and A.S.P.E.N Nutrition Support Practice Manual 2nd Edition15

Regarding access in EN, nasogastric (NG) feedings may be initially tried, however if

patients are experiencing oral/esophageal GVHD or mucositis/esophagitis, NG tubes

should not be used. Postpyloric access may be indicated in patients with delayed gastric

emptying or frequent emesis.15 Percutaneous endoscopic gastrostomies (PEGs) are only

indicated when a patient in no longer in a neutropenic state since it requires surgery.

According to A.S.P.E.N. guidelines, patients must have platelets >50,000 units/L and

absolute neutrophil counts >1000/mm3 as patients with numbers below this are in a

neutropenic state. Patients in a neutropenic state are more susceptible to infections from

surgery. Sometimes PEGs are placed two to three weeks prior to the conditioning

treatment and transplant as a way to allow the body to heal from the surgery and provide

a means to prevent malnourishment.

31

According to the A.S.P.E.N. guidelines, “PN is associated with improved long-term

disease-free survival compared to hydration support in allogeneic patients receiving

myeloablative conditioning regimens.”15 Indications for PN are listed in Table IV and

supported in Table XV in which nutritional management of GI GVHD is described. Most

patients have dual-lumen central venous access for several months post transplant in

order to administer intravenous medications and blood products.15 As such, PN is often

the first line of defense in a malnourished post-SCT patient due to the easy access of the

central line. Some complications with PN include hyperglycemia, hypertriglyceridemia,

essential fatty acid deficiency, cholestasis and gallbladder sludge, and infections.15

Glucose monitoring is especially important in patients receiving PN, and high doses of

insulin may be necessary to control levels, especially when patients are on

corticosteroids. Proper glucose control will help “decrease the number of bloodstream

infections, renal failure requiring dialysis/filtration, red blood cell transfusions, and

mortality.”20

IV. TREATMENT SIDE EFFECTS AND NUTRITIONAL INTERVENTIONS

A. Mucositis and Esophagitis

Mucositis and esophagitis are an expected complication of myeloablative conditioning.15

Mucositis is the inflammation of the oral mucosa from chemotherapy or radiation and

presents itself in the form of ulcerations or erythema (redness/rash of the skin). Mucositis

normally arises in 7-10 days after chemotherapy treatment begins and can cause a

significant decrease in intake due to the pain it causes.

32

Esophagitis is inflammation, redness and possible ulcerations within the esophagus. The

degree in which patients experience symptoms is based on how intense the conditioning

treatment is. The development of mucositis or esophagitis takes place over four phases:

“an inflammatory phase caused by the release of cytokines during conditioning therapy;

an epithelial phase, when cells cease dividing and die; an ulcerative phase when

microbes and endotoxins translocate into the bloodstream; and a healing phase, which

can be prolonged with deep lesions and is more complex in the gut than in the mouth.”26

Patients say that mouth pain associated with mucositis is the “most debilitating” side

effect of SCT and it is normally one of the first symptoms to occur.15, 26 The pain often

leads to the patient completely forgoing food and fluid intake, often leading to acute

weight loss and dehydration.19 A thorough assessment of the mouth is necessary, as

“alterations in the oral mucosa may include color changes of the tongue, lips, and

gingiva; changes in moisture; and changes in integrity, including cracks, fissures, ulcers,

blisters and lesions.”19 Opioids are normally used to treat the pain. Methotrexate, which

is used to prevent GVHD, can exacerbate the ulcerations and pain.15 Mucositis is

normally the first symptom post-SCT, often appearing within a week of the transplant as

33

neutrophil count drops significantly low. “Healing begins with marrow engraftment

(absolute neutrophil count >500/cm3)” which takes about 7-14 days after first

appearing.15

Table V. MNT for Mucositis and Esophagitis,23 Mucositis and Esophagitis

• Try soft or pureed foods • Try a blenderized liquid diet – high calorie/high protein smoothies • Offer smooth, bland, moist foods (custards, cream soups, yogurt, mashed potatoes) • Offer soft, nonirritating, cold foods (popsicles, ice cream, frozen yogurt, slushes) • Encourage frequent mouth rinsing to remove food and bacteria and to promote healing • Avoid salty, spicy, and acid foods • Avoid rough-textured foods • Avoid alcohol and carbonated beverages • Avoid extreme temperatures in foods

B. Xerostomia and Dysgeusia

Xerostomia – in which saliva production decreases and saliva becomes viscous – occurs

due to myeloablative regimens, antiemetics, antidepressants, and opiate-containing pain

medications.15 Dysgeusia, which is impaired taste, and hypogeusia, which is diminished

taste, occur most often due to the conditioning treatments and are prolonged due to

morphine and antibiotic medications. Altered salivation often precipitates dysgeusia

because saliva is needed for taste perception. Medical nutrition therapy for these

conditions involves the goal of comfort for patients who are in pain and creating a desire

to eat despite difficulty chewing and tasting foods.

Table VI. MNT for Xerostomia and Dysgeusia Xerostomia

• Moist foods (stews, casseroles, canned fruits) and liquids • Add extra sauces, gravies, margarine, butter and broth to foods • Encourage liquid with meals • Add vinegar or pickles to foods (this induces salivation) • Offer lemon-flavored, sugarless candy to help stimulate saliva • Encourage good oral hygiene • Try commercial saliva substitutes • Offer clear liquids (tea, popsicles, slushes, warm broth)

34

Dysgeusia • Try different flavors and spices to find acceptable ones • Meats may be problematic and require alternate flavoring or preparation • Add lemon or lime slices to water • Dilute juices or other fluids if too sweet • Use plastic utensils instead of metal if a metallic taste is present

C. Nausea and Vomiting

Nausea and vomiting are very common side effects of the conditioning treatment,

supportive care medications (antibiotics, cyclosporine, interleukin-2, trimethoprim-

sulfamethoxazole, and mycophenolate mofetil), GI infections, intestinal GVHD, and fluid

and electrolyte imbalances.15 Antiemetics are often administered to treat and prevent

nausea and vomiting. These are normally given via IV when symptoms are occurring and

then given orally as symptoms improve.

Table VII. MNT for Nausea and Vomiting15, 19, 23

• A clear liquid diet may be indicated if symptoms are severe • Try high-carbohydrate foods and fluids (crackers, toast, gelatin) as well as nonacidic

juices – electrolyte-replenishing drinks are often indicated • Antiemetics should be taken 30-45 minutes before a meal • Try small, frequent meals • Offer cold, clear liquids and solids • Avoid overly sweet or high-fat foods • Create a comfortable setting when eating • Avoid strong or unpleasant odors • Encourage adequate fluid intake • Avoid offering the patient’s favorite food during periods of nausea, as it may cause a

permanent dislike of the food • Document foods/smells/events that may trigger nausea and try to avoid them when

possible D. Diarrhea and Steatorrhea

Diarrhea is often due to myeloablative treatments, antibiotics, intestinal infections, GI

GVHD, lactose intolerance, and GI mobility agents. “Liver and intestinal GVHD may

produce steatorrhea and fat malabsorption.”15 Diarrhea will normally occur within the

first two weeks post-SCT as a result of the toxicity to the GI mucosa during the

conditioning treatment, but should resolve itself if no other problems appear. After the

35

two week mark, if diarrhea occurs it is normally a sign of GI GVHD or an infection20. It

is important to monitor daily stool output, as diarrhea >500 mL/day is an indication for

parenteral nutrition support.

Table VIII. MNT for Diarrhea and Steatorrhea15, 20, 23 • Try a low-fat, low fiber diet • Avoid caffeine • Offer cold or room-temperature foods and beverages as they may be better tolerated • Offer low lactose intake • Encourage adequate fluids and electrolyte intake to prevent dehydration • Avoid excessive fruit juice ingestion • If large volume diarrhea occurs, add zinc to the PN solution • Monitor copper levels and add to PN if needed

E. Early Satiety and Appetite Loss

Early satiety is a symptom of MF, as the enlarged splenomegaly causes pain/fullness

below the ribs on the left side, which leads to a feeling of fullness and therefore loss of

appetite. It can also be caused by delayed gastric emptying in patients post-SCT. In

addition, the conditioning treatments (chemotherapy and radiation) often lead to appetite

loss due to nausea. In general, patients simply do not feel inclined to eat, as they either

do not feel hungry or food no longer appeals to them.

Table IX. MNT for Early Satiety and Appetite Loss15, 20, 23 • Small, frequent meals • Nutrient dense foods • Create a comfortable, appealing environment when eating • Avoid foods that cause aversions • Avoid favorite foods as to avoid creating aversions • Try smoothies, shakes, protein powders, added fats • Prokinetics may be indicated for delayed gastric emptying

F. Anorexia

Anorexia, which is the lack of or loss of appetite for food, occurs from a variety of

symptoms. Overall loss of appetite may occur during the conditioning treatment and

immediately post-transplant and it may be related to each of the symptoms listed above. If

a patient is experiencing severe mouth pain or no longer enjoys the taste of foods, oral

36

nutrition is likely to decrease. Early satiety will also result in decreased energy intake.

Nausea, vomiting, and diarrhea will create a malnourished state that can mimic the

symptoms of anorexia. According to A.S.P.E.N., “prolonged use of PN post-SCT has

been associated with anorexia and delayed resumption of oral intake.”15

Table X. MNT for Anorexia15, 23

• Offer small, frequent meals of nutrient-dense foods • Maximize intake when appetite is most normal • Limit fluids with meals to avoid feeling full • Use carbohydrate supplements and protein powders • Create a pleasant mealtime environment with enhancing food aromas, colorful place

settings, and foods with varied colors and textures • Assess nutritional status through calorie counts

G. Liver Complications (SOS)

Sinusoidal obstructive syndrome, is a syndrome of “jaundice, weight gain, ascites and

painful hepatomegaly developing within approximately 10-20 days after SCT.”20

Medical nutrition therapy for SOS mainly involves restricting fluid and sodium intake.

Therefore, patients receiving nutrition support should receive concentrated solutions

without added sodium; for those who are eating orally, sodium should be restricted.

Dietitians and pharmacists should work together to evaluate whether a patient can

receive his/her medications via a dextrose-based solution rather than through IV

solutions with sodium. When a patient has severe SOS and liver failure, copper and

manganese levels need to be monitored since excessive blood levels can be toxic if

biliary excretion is abnormal.20 In addition, iron should be monitored as patients with

SCT receive many iron-containing blood products throughout their treatment. Iron

overload can lead to hemosiderosis of the liver.

Table XI. MNT for SOS20 • Limit/eliminate sodium and fluid intake • Monitor copper and manganese – eliminate if elevated • Avoid iron supplements and iron-containing multivitamins

37

H. Renal Complications

Renal complications arise from a variety of factors. The conditioning treatment may

cause kidney damage, medications (cyclosporine, tacrolimus, amphotericin,

aminoglycosides, vancomycin, and trimethoprim-sulfamethoxazole) are associated with

renal damage and insufficiency, and damage may be part of SOS as heptorenal failure.

Table XII. MNT for Renal Complications15, 20, 23 • Maintain sufficient intravascular volume • Correct electrolyte imbalances • If the patient receives hemodialysis:

o Monitor Vitamin A status, as it is known to accumulate during renal failure o Provide a complete complex of water-soluble vitamins and folic acid o Ensure Vitamin K needs are met o Provide additional protein to compensate for losses during filtration o Control glucose levels o Replete calcium and magnesium if levels are low

I. Infections

After taking a variety of immunosuppressive medications prior to the SCT, neutrophil

counts are severely decreased, which means that the patient is in a state of

immunosuppression. The state of immunosuppression is important in order to allow the

new donor cells to establish themselves inside the body of the recipient without being

rejected. During this period, the patient is at an increased risk for infection since there

are not enough white blood cells to fight off foreign bacteria and harmful organisms. The

medical nutrition therapy for this condition is the neutropenic (i.e. low bacteria) diet.

The neutropenic diet is designed to reduce the risk of food-borne illness (food

poisoning) in individuals whose immunity is low due to low white blood cell counts.

There is not much evidenced-based research to support neutropenic diets; however, it

remains a common practice to recommend following this diet as long as a patient is

taking immunosuppressant medications including cyclosporine, tacrolimus,

38

methotrexate, and prednisone (in other words, as long as it is thought that the patient is

still in an immune-compromised state).28 A.S.P.E.N. states that “Patients should receive

dietary counseling regarding foods that may pose infectious risks and safe food handling

during the period of neutropenia.”25 The following is a basic outline on a neutropenic

diet provided by the Leukemia and Lymphoma society.29 A more detailed version can

be found in the Appendix.

Table XIII. MNT for Neutropenia27 • Avoid all uncooked vegetables and most uncooked fruits. You may eat fruit that you

can peel a thick skin off of, such as a banana or an orange. Cooked vegetables and canned fruits and juices are safe to eat.

• Avoid raw or rare meat and fish and uncooked or undercooked eggs. Cook meat until it's well-done. Thoroughly cook eggs (no runny yolks).

• Avoid salad bars and deli counters. Buy vacuum-packed lunch meats instead of freshly sliced meats.

• Consume only pasteurized milk, yogurt, cheese and other dairy products. • Avoid soft mold-ripened and blue-veined cheeses such as Brie, Camembert, Roquefort,

Stilton, Gorgonzola and Bleu. • Avoid well water or boil it for one minute before drinking. At home, it's okay to drink

tap water or bottled water. V. GVHD AND NUTRITIONAL INTERVENTIONS

As noted above, the four types of GVHD include skin, oral, GI, and liver. The first line of

defense against GVHD is medications – immunosuppressants such as cyclosporine, methotrexate

and tacrolimus, steroids like prednisone, and pain medications including opioids. The impact that

GVHD has on nutritional needs is usually significant but very difficult to manage. In general,

“needs are increased due to hypermetabolism, tissue damage, fluid and electrolyte imbalances,

and medication-induced effects.”15 Energy needs are normally at the higher end of the 30-50

kcal/kg range, however intake is normally significantly reduced due to the symptoms described

above. Protein needs are especially increased to 1.5-2 g/kg when there is tissue damage, with the

higher end usually reserved for those with severe GVHD.23 Cases of severe GVHD (especially

39

when in stage 3 or 4, see Table XIV below) are often indicators for EN or PN. GVHD can be

diagnosed with a biopsy of the area affected.

Table XIV. Staging of Acute GVHD Skin Liver GI Tract Stage 1: <25% rash Stage 2: 25-50% rash Stage 3: generalized erythroderma Stage 4: bullae (blisters)

Stage 1: bili 2-3 mg/dL Stage 2: bili 3.1-6 mg/dL Stage 3: bili 6.1-15 mg/dL Stage 4: bili >15 mg/dL

Stage 1: diarrhea > 500 mL/day Stage 2: diarrhea > 1000 mL/day Stage 3: diarrhea > 1500 mL/day Stage 4: ileus, bleeding

According to A.S.P.E.N. Guidelines “nutrition support therapy is appropriate for patients

undergoing hematopoietic cell transplantation who develop moderate to severe graft-vs-host

disease accompanied by poor oral intake and/or significant malabsorption.”25 While indicated in

order to keep a patient nourished when oral feedings are not possible, PN has been associated

with an increased incidence of GVHD due to decreased oral intake.25, 31 Although not thoroughly

understood, studies have shown that the incidence of GVHD (especially GI GVHD) decreases

with a standard oral diet or with EN.32 The following reviews the types of GVHD and the

nutritional management if applicable.

A. Oral GVHD

Mucositis is a major sign of oral GVHD and are extremely painful, often leading to

significantly decreased energy intake.

B. Skin GVHD

This is characterized by a severe rash anywhere on the skin, specifically by a “pruritic,

maculopapular, and erythematous rash.” If it advances, it can sometimes turn into ulcers,

blisters and worse that may lead to the need for burn care. If chronic, it can lead to

changes in skin color.15

40

C. Liver GVHD

“Liver GVHD presents as cholestasis, elevated alkaline phosphatase and serum bilirubin

levels, jaundice, hepatomegaly, and, in severe cases, encephalopathy and hepatorenal

failure.”15 This complication can be fatal.

D. GI GVHD

GI GVHD can affect the GI tract anywhere from

the esophagus to the rectum. It can cause

difficulty swallowing, nausea, vomiting,

abdominal cramps, poor absorption of nutrients

(including fat and protein malabsorption),

problems with gut motility, weight loss, and

diarrhea. GI GVHD can be life threatening in its

effects on the GI tract, including GI bleeds,

ulcerations, and mucosal sloughing.15 A.S.P.E.N.

has created guidelines for the management of GI GVHD that can be followed in clinical

practice.15 It is important to note that probiotic therapy – which is normally indicated in

patients with diarrhea as it adds good mucosal bacteria to the GI tract – is not indicated in

patients with GI GVHD.20

Table XV. Nutritional Management of GI GVHD15 Phase Clinical Symptoms Diet Nutrition Support

1. Bowel rest GI cramping Large-volume watery

diarrhea or active GI bleeding

Depressed serum albumin Severely reduced transit

time Small-bowel obstruction or

diminished bowel sounds Nausea and vomiting

Oral: NPO PN with supplemental zinc and possibly copper

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2. Introduction of oral feedings

Minimal GI cramping Diarrhea <500 mL/day Improved transit time

(minimun 1.5 hours) Infrequent nausea and

vomiting

Oral: isomotic, low-residue, low-lactose beverages, initially 60 mL every 2-3 hours, for several days

PN Trophic* enteral feeds of

semielemental formula if patient is unable to eat

3. Introduction of solids

Minimal or no GI cramping Formed stool

Oral: allow introduction of solid food, once every 3-4 hours: minimal lactose, low fiber, low fat (20-40 g/day), low total acidity, no gastric irritants

Begin to cycle and decrease PN

Advance feeds slowly (small boluses or continuous infusion) if patient is unable to eat

4. Expansion of diet

Minimal or no GI cramping Formed stool

Oral: minimal lactose, low fiber, low total acidity, no gastric irritants; if stools indicate fat malabsorption: low fat

Nighttime supplemental PN if oral intake is less than needs or patient is unable to maintain weight owning to malabsorption

Enteral feed schedule and formula are dependent on any residual GI symptoms

5. Resumption of regular diet

No GI cramping Normal stool Normal transit time Normal albumin

Oral: progress to regular diet by introducing 1 restricted food per day: acid foods with meals, fiber-containing foods, lactose-containing foods. The order of addition will vary depending on individual tolerances and preferences

Patients no longer exhibiting steatorrhea should have the fat restriction liberalized slowly

Discontinue PN Supplemental enteral feeds if

patient unable to eat adequate nutrients

*Trophic feeding is “a small volume of balanced enteral nutrition insufficient for the patient's nutritional needs but producing some positive gastrointestinal or systemic benefit”20. It is commonly used in the pediatric population. VI. NUTRITION CARE PROCESS

The A.S.P.E.N. Clinical Guidelines for “Nutrition Support Guideline Recommendations in

Hematopoetic Cell Transplantation” states the following: “All patients undergoing hematopoietic

cell transplantation with myeloablative conditioning regimens are at nutrition risk and should

undergo nutrition screening to identify those who require formal nutrition assessment with

development of a nutrition care plan.”25 The Patient Generated Subjective Global Assessment

(PG-SGA), as shown in the Appendix is a nutrition screen that can be used on oncology patients

to assess their nutritional status. It has been “shown to be accurate at distinguishing well-

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nourished patients from malnourished patients, and has a high sensitivity and specificity. It is a

quick, valid, and reliable nutrition assessment tool that enables malnourished hospital patients

with cancer to be identified and triaged for nutrition support.”19 The PG-SGA is a good starting

point for an assessment, however a more thorough and comprehensive assessment is needed

initially and continually throughout treatment, as changes in nourishment can happen rapidly in

the SCT population.

A. Nutrition Assessment

1. Food/Nutrition-Related History

This includes the subjective evaluation of current food and nutrient intake,

including allergies and intolerances, current medications and supplements,

alternative medicines, nutrition knowledge, attitudes towards food/nutrition, food-

related beliefs and behaviors, factors that affect access to food and medications,

and physical activity.19 Understanding these factors helps assess where the patient

is in their knowledge of food and nutrition in relation to health in general and

their disease state, and it also helps to understand their willingness to change

certain behaviors. For cancer patients specifically, this should reveal any potential

impediments to food intake and tolerance. Past dietary treatment of the current

disease – or any other disease states – should be recalled, along with the success

and failures of those treatments. Dietitians should look at past use of enteral

nutrition (EN), parenteral nutrition (PN), supplementation, and fluid intake. For

patients with myelofibrosis, this information will help the dietitian later determine

how to approach specific interventions. Specifically for dietitians treating patients

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with MF who are treated with SCT should evaluate the following prior to, during

and after treatment:15

• Chewing/swallowing difficulties • Mucositis and esophagitis • Dental health • Taste alterations • Xerostomia • Heartburn or reflux • Nausea and vomiting • Early satiety • Appetite changes – calorie counts/food diaries may be necessary • Anorexia • Changes in bowel habits

2. Anthropometric Measurements and Nutrition-Focused Physical

Findings

Anthropometric measurements are crucial in assessing patients with MF, as

weight loss >10% over 6 months is one of the main constitutional symptoms used

in the diagnosis process. In addition, weight loss is a major effect of

chemotherapy, radiation and SCT due to diarrhea, vomiting, nausea, early satiety,

chewing/swallowing difficulties, and taste alterations. The following should be

assessed initially, during treatment and after treatment in patients with MF:

• Height • Weight • BMI • IBW • %IBW • Weight change over the past 1 month, 6 months, 1 year

(voluntary/involuntary?) • %UBW • Skinfold measurements (subcutaneous fat) • Mid-arm muscle circumference (lean body mass) • Edema

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In cancer patients, weight should be evaluated throughout treatment based on the

patient’s usual body weight; it should not be evaluated using a reference standard

such as ideal body weight. While changes in weight are often the most visually

and numerically obvious changes and should certainly be a main focus, weight

alone does not tell the entire story of the patient’s nutrition status. For instance,

patients may experience significant fluid retention due to medications leading to

ascites and/or edema. In this case, it is important to analyze the time frame of the

weight change and look at physical changes in the patient’s body. Mid-arm

muscle circumference along with skinfold measurements can help determine

whether a patient is losing fat-free or fat mass, an important consideration in

determining malnutrition.

3. Biochemical Data, Medical Tests and Procedures

Laboratory data for patients with MF and patients who undergo SCT should be

assessed throughout a patient’s lifetime, as changes can signify changes in disease

state and nutritional status and will therefore affect the treatment course. Below

are a list of the common tests and procedures used to help diagnose and

continually assess patients with MF, along with their normal lab values and what

the patients values can tell us about their disease state:

Lab Normal Range Likely Cause Red Blood Cells (RBCs)

M: 4.7-6.1 million/mm3

F: 3.9-5.5 million/mm3 Increased in polycythemia, dehydration, severe diarrhea Decreased in anemia, Fe deficiency, systemic disease (i.e. leukemia)

White Blood Cells (WBCs)

3200-10,600/ulq Increased in leukemia, bacterial infection, hemorrhage, trauma or tissue injury, cancer Decreased in viral infections, chemotherapy, radiation, bone-marrow depression

Platelets 177-406 x 1000/uL thrombocytosis thrombocytopenia

Increased in malignancy (i.e. leukemia), polycythemia vera, post splenectomy, iron deficiency anemia Decreased in hemolytic/pernicious anemia, chemotherapy, infection, leukemia

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Neutrophils >1,000/mm3 Low neutrophils due to immunosuppression Glucose Fasting: 70-99 mg/dL Increased in diabetes, high blood sugar

Decreased in hypoglycemia Albumin 3.5-5.0 gm/dL Increased in dehydration

Decreased in edema, hepatic disease, malabsoption, diarrhea, malnutrition, low protein intake, over-hydration, some cancers

Prealbumin 18-38 mg/dL Increased in renal failure Decreased in acute catabolic state, hepatic disease, stress, infection, surgery, malnutrition, low protein intake

Magnesium 1.3-2.1 mEq/L Increased in diarrhea, steatorrhea, malasbsorption syndromes, medications (amphotericin, cyclosporine; foscarnet; tacrolimus), refeeding syndrome, severe malnutrition Decreased in discontinuation of magnesium-wasting medication, excessive supplementation, renal insufficiency, malabsorption, malnutrition

Potassium 3.5-5.5 mEq/L Increased in GI losses, medications (amphotericin; corticosteroids; furosemide; foscarnet), refeeding syndrome, anabolism Decreased in excessive supplementation, potassium-sparing diuretics, renal insufficiency, tacrolimus

Sodium 136-144 mEq/L Increased in excessive GI losses, dehydration, fluid retention, excessive IV or oral fluid/free water intake, hyperglycemia, medications (cyclophosphamide; cyclosporine; furosemide) Decreased in inadequate fluid replacement during GI losses, aggressive diuretic therapy, fever

Phosphorus 2.3-4.3 mg/dL Increased in diabetes, medications (corticosteroids; cyclophosphamide; foscarnet; sirolimus), refeeding syndrome, renal acidosis, steatorrhea Decreased in excessive phosphorus intake, multiple myeloma, myelogenous leukemia, renal failure

Calcium 8.4-10.2 mg/dL Increased in medications (corticosteroids; foscarnet; pamidronate), vitamin D deficiency Decreased in lymphoma, metastatic breast cancer, multiple myeloma, renal failure

Creatinine 0.4-1.2 mg/dL Increased in renal disease, muscle damage, starvation, diabetic acidosis

BUN 8-23 mg/dL Increased in renal failure, dehydration, infection, diabetes, excessive protein/catabolism Decreased in malnutrition, hepatic failure, malabsorption, overhydration

ALT M: 4-40 U/L F: 4-31 U/L

Increased in liver dysfunction

AST M: 10-37 U/L F: 10-31 U/L

Increased in liver dysfunction

Triglycerides (fasting range, mg/dL) desirable <150 borderline 150-199 high 200-499 very high >500

Increased in hyperlipidemia from PN, hepatic disease, poorly controlled diabetes Decreased in malnutrition, malabsorption syndrome

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4. Patient History

Assessing the patient’s history, including socioeconomic status, education level,

social support systems, family situation, lifestyle and attitude towards their

disease state will all affect nutrition status, both in the short term and long term. It

is important to understand if a patient has the ability to follow nutrition

recommendations outside of the hospital setting, which could strongly be affected

by their economic status and support systems. Their attitude towards their disease

state and nutrition recommendations may help one evaluate where the patient is in

his/her readiness to learn. A patient’s prognosis and medical course are also

extremely important factors to consider when giving nutrition recommendations.

For instance, if a patient’s goal is comfort versus survival and palliative care is

involved, it would be important to understand where the patient stands in

receiving alternate forms of nutrition support through parenteral or enteral

nutrition. All of these factors will influence the interventions and goals set later in

the nutrition care process.

B. Nutrition Diagnosis

Nutrition diagnoses are often subjective and can vary from day to day depending on the

nutritional status of the patient and the intervention priority, especially in the oncology

population. As a patient’s condition evolves, so does the diagnosis. Diagnoses and

interventions should be discussed with other areas of the medical team such a nurse

practitioners, doctors, nurses and speech pathologists in order to assess how realistic an

intervention is. The following are examples of possible diagnoses throughout the course

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of treatment for a patient with MF treated with SCT along with the potential reasons for

the diagnosis (this list does not cover all potential diagnoses/causes):

• MF patients prior to treatment: o Inadequate energy intake – related to early satiety from splenomegaly o Unintended weight loss – related to inadequate intake from nausea or

fatigue from low red blood cells o Excessive iron intake – related to increased iron levels from red blood

cell transfusions • During conditioning treatments:

o Inadequate energy intake – related to increased needs and/or nausea/vomiting, early satiety, anorexia, taste changes

o Unintended weight loss – related to increased needs from hypermetabolism

o Increased nutrient needs – related to altered absorption (from N/V/D/C)

o Altered nutrition-related labs (glucose levels) – related to steroid medications and/or nutrition support

• Post-SCT:

o Inadequate energy intake – related to increased needs and/or nausea/vomiting, early satiety, anorexia

o Inadequate protein intake – related to increased needs for tissue repair o Altered nutrition-related labs – related to electrolyte imbalances from

emesis and diarrhea o Excessive fat intake – related to decreased needs from

diarrhea/steatorrhea o Altered GI function – related to GI GVHD o Chewing/swallowing difficulty – related to oral GVHD o Food- and nutrition- related knowledge deficit – related to neutropenic

diet

C. Nutrition Intervention

1. Prioritizing Diagnoses and Indentifying Goals

The intake domain remains the most important area to tackle for a dietitian. It can

often be the most acute problem, especially in oncology patients, and therefore it

is commonly the most urgent. Weight changes are also extremely important to

note in this population, as changes in weight often signify an underlying problem

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such as hypermetabolism, inadequate intake, or inability to consume sufficient

nutrients orally.

Two aspects of the SCT population make it somewhat difficult to prioritize

diagnoses. The first is that changes can take place so acutely that the most

important diagnosis one day may differ from the most important diagnosis the

next. For instance, a patient may have mucositis on Monday in which the goal

might be to consume at least one high calorie nutritional supplement drink a day.

Then Tuesday the patient may develop excessive diarrhea and nausea – in which

the intervention would likely be to remain NPO until symptoms resolve – all

while the mucositis still remains. The point is that goals may change daily and

close monitoring is extremely important in this population.

The second aspect – which is somewhat of a continuation of the first – is that

multiple diagnoses may present themselves at once and it is up to the dietitian to

prioritize based on experience and knowledge. Continuing with the previous

example, during this time of mucositis, diarrhea and nausea, nutrition-related lab

values may be altered as a side effect of these conditions and medications in

which the goal may be to replete electrolytes and try to normalize lab values.

Furthermore, a week later the patient may show signs of severe weight loss from

the inadequate intake and increased needs in which the goal would be to increase

intake and weight. The priorities and interventions will continually and quickly

change based on the patient’s condition and needs.

Interdisciplinary practices are extremely important in order to prioritize goals. It is

the job of the RD to convey the importance of nutritional care during this time to

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other disciplines. In addition, it is just an important for the RD to understand the

goals of care of the other disciplines in order to understand what are realistic

interventions for the patient.

2. Planning and Implementing the Nutrition Intervention

Interventions for this patient population are discussed above in the section

“Symptoms and Nutritional Interventions.” When implementing these

interventions, it is important to discuss any dietary changes with the medical team

in order to make sure nutritional and dietary goals are consistent with the medical

goals. It is also important to educate the patient on the changes being made, as this

will help with educating the patient on nutritional guidelines and will likely

contribute to better compliance.

D. Nutrition Monitoring and Evaluation

1. Food/Nutrition-Related History Outcomes

Monitoring food intake will be one of the most important parts of this process. If a

patient is in the hospital, interviewing is an efficient way of monitoring intake. If

the patient were unable to convey his or her food intake, a 3-day calorie count

conducted by a nurse would be a good option. When discharged from the hospital,

SCT patients must follow up weekly with an outpatient doctor over an extended

period of time. During these appointments, intake should be assessed along with

food tolerance, diet adherence, physical activity, food supplies and availability,

and overall nutritional quality of life.

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2. Anthropometric Measurement Outcomes

The following measurements should be continually assessed throughout treatment

and after treatment for an extended period of time to be determined by the

medical team:

• Height • Weight • BMI • IBW • %IBW • Weight change over the past month, 6 months, 1 year • %UBW • Skinfold measurements (subcutaneous fat) • Mid-arm muscle circumference (lean body mass) • Edema

In addition, nutrition-focused physical findings should be assessed, such as

physical appearance, muscle and fat wasting, and swallow function.

3. Biochemical Data

The same labs noted above under “Biochemical Data, Medical Tests and

Procedures” should be assessed continually throughout and after treatment.

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PRESENTATION OF THE PATIENT Patient: MS, 47 year old male Admission date: November 7, 2012 Current diagnosis: Myelofibrosis (MF), Jak2 V617F mutation positive Duration of present illness: 8 years from diagnosis Admitted for: Allogenic stem cell transplantation (allo-SCT) Past medical history: MS was diagnosed with MF – Jak2 mutation positive in 2004 when he presented with a ruptured spleen after a snowboarding fall. He was seen at Winthrop in Long Island where he had a bone marrow examination and was diagnosed with MF. From diagnosis to May 2012, MS was treated with long-course hydroxyurea (HU) 1,000 mg/day. Throughout his treatment, he had transfusion-dependent anemia and marked splenomegaly. From May to August 2012, his therapy was switched to Jakafi 15 mg twice a day. In August 2012 his counts dropped significantly and the medication was discontinued. He was then admitted to Winthrop with fever and severe anemia. He received a packed red blood cell (PRBC) transfusion and was placed on low dose Jakafi which he took until 11/6/12. He has an 10/10 HLA identical sibling and was referred to MSH for allo-SCT. Family history: no relevant family history Social history:

• Married with three children • Works as a high school teacher • Non-smoker, denies alcohol/drug use • Strong familial support system

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MEDICAL AND NUTRITIONAL HOSPITAL COURSE MS was admitted to Mount Sinai on November 7, 2012 specifically for stem cell transplantation treatment. He was treated for 7 days with a combination of Fludarabine and Busulfan for his chemotherapy conditioning. After a day of rest (D-1), he received the stem cell transplantation infusion from his brother. Of note, MS has four brothers and one was a 10/10 HLA match. His brother’s cells were harvested peripherally the same morning of transplantation (#D 0), processed the same day, and then administered into MS. The below description navigates through MS’s hospital course with the nutritional interventions in ADIME note form throughout. MS’s hospital stay was from November 7-December 3, 2012. Nutrition saw him weekly throughout his stay. He continues to follow-up weekly in an outpatient clinic to monitor his engraftment. The medications used are described in the “Medication Bibliography” section under “Patient Medications.” Events post-discharge are described in the “Summary Section” below. November 7: #Day-8

• Admission • Hickman catheter placed • Chemotherapy plan:

o Conditioning: ! Fludarabine (Fludara) – Flu ! Busulfan (Busulfex) – Bu

o Post-SCT ! Methotrexate (MTX)

• Physical findings: palpable splenomegaly • Conditioning Schedule:

o D-7: Flu + Bu o D-6: Flu + Bu o D-5: Flu + Bu o D-4: Flu o D-3: Flu o D-2: Flu o D-1: Rest day o D 0: SC infusion

• GVHD/Immunosuppression: Tacrolimus from D-1 and MTX IV on D+1, D+3, D+6 • Medical goals during treatment:

o To be discharged home, engrafted and clinically well November 8: #D-7

Initial Nutrition Assessment Assessment: 48 y/o M with dx of MF since 2004, treated with HU then Jakafi until 8/12 when his counts dropped significantly; was then admitted to Winthrop with fever and severe anemia. Admitted to MSH 11/7 for allo-SCT from HLA-identical sibling. Noted conditioning treatment begins today. Visited pt at bedside with wife present. Pt

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reports fair appetite since admit (does not enjoy hospital food but eats meals brought in by wife). Pt is with no complaints of nausea/vomiting or chewing/swallowing difficulty at this time, no recent wt loss (UBW=~190#). Pt reports loose stool x1 today. Pt follows a regular diet at home. NKFA. BMT Day#: -7 Diet: Low Bacteria Supplements: None Relevant labs: Ca 8.4 Notable meds: acyclovir, levaquin, ondansetron, dexamethasone Chemo: fludarabine, busulfan Skin: no breakdown noted Ext: no edema noted Anthropometrics Ht: 1.81m (71”) Wt: 85 kg (187#) IBW: 78 kg (+/- 10%) %IBW: 109% BMI: 26 Estimated Nutritional Needs: Kcal: 2120-2550 kcal/day (25-30 kcal/kg) Pro: 102-128 g/day (1.2-1.5 g/kg) Nutrition Diagnosis: 1. Food- and nutrition-related knowledge deficit related to lack of prior exposure to accurate nutrition information

as evidenced by no prior knowledge of low bacteria diet s/p chemo and SCT. Pt at moderate nutrition risk secondary to chemotherapy treatment initiation and need for neutropenic diet. Pt appears normal weight consistent with BMI 26. Continue with Low Bacteria diet. Extensive low bacteria diet education was given; pt and wife asked appropriate questions and demonstrated good understanding; compliance is expected. Will reinforce before discharge. Nutrition Interventions: 1. Continue with low bacteria diet 2. Provided written and verbal low bacterial diet education 3. Provide supplement as needed 4. Low Ca noted, replete as medically appropriate 5. Encourage good po and fluid intake Monitor/Evaluation: 1. Anthropometrics, labs, po intake and diet tolerance, nutrition-focused physical findings, BM November 13: #D-2 MS began experiencing diarrhea 1-3x/day with nausea and little appetite. He was given Immodium to help with the diarrhea.

Nutrition Follow Up

Previous nutrition note reviewed. Pt reports feeling tired with no appetite, poor po intake (only ate soup yesterday brought in by wife). Soup provides ~400 kcals, 8 g protein. Pt with complaints of some nausea, diarrhea 1-3x/day. Pt denies vomiting, no chewing/swallowing difficulties at this time. Pt not consuming shake. BMT Day#: -2

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Diet: Low bacteria Supplements: shake - whole milk, ice cream, beneprotein Labs: Ca 8.3 Notable meds: acyclovir, levaquin, ondansetron, immodium, methylprednisolone Chemo: fludarabine Skin: no breakdown noted Anthropometrics Wt (11/13): 86.8 kg Admitted wt (11/7): 83.7 Wt change: 3.7% gain in 6 days Nutrition diagnosis: Inadequate oral intake related to nausea, diarrhea, and appetite loss from high dose chemotherapy as evidenced by consumption of <25% of nutritional needs. Nutrition Interventions: 1. Continue with low bacteria diet 2. Pt not consuming shakes 2/2 nausea and diarrhea; will discontinue shakes 3. Reviewed food options consistent with Low Fiber diet and encouraged to increase po intake as able 4. Noted pt on Immodium – would continue until diarrhea resolves 5. Wife to track po intake 6. Encourage fluid intake Monitor/Evaluation: 1. Anthropometrics, labs, po intake and diet tolerance, nutrition-focused physical findings, BM November 15: #D-0 Stem cell infusion day

• MS began feeling better overall with improved nausea. However, he began experiencing drenching night sweats during the night and had a rash over his back for two nights. He denied fevers, chills, and abdominal pain at this time. He still remained with palpable splenomegaly at this point. Any nausea he was feeling was likely due to Fludarabine and was being controlled by Ativan and Zofran. Received Benadryl for rash on back which helped with significant improvement.

• MS was seen by Dermatology who noted “rash is mildly pruritic but not otherwise bothersome.”

November 20, 2012, #D+5 #D+5: Mucositis pain developed. Palliative care intervened and added a morphine drip.

Nutrition Follow Up Previous nutrition note reviewed, diarrhea has resolved at this time. Pt reports feeling okay with increasing appetite, fair po intake (cornflakes for breakfast x2, canned soup for lunch, hospital dinner). Pt with some complaints of pain when swallowing 2/2 sores on tongue. Per NP note, pt with mucositis. Pt with no complaints of N/V/D/C, +BM today. BMT Day#: +5 Diet: Low Bacteria Supplements: adding shake - vanilla soy milk, banana, 2 packets beneprotein Labs: neutrophils 0.5 Meds: prograf, tacrolimus, magic mouthwash, cancidas

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Anthropometrics Wt (11/20): 82.8 kg Wt (11/13): 86.8 kg Wt change: 4.6% x1 week (significant) Nutrition diagnosis: Unintended weight loss related to diarrhea and appetite loss likely from high dose chemo and SCT as evidenced by significant weight loss of 4.6% loss x1 week. Nutrition Interventions: 1. Continue with low bacteria diet 2. Provide supplement: shake (vanilla soy milk, banana, 2 packets beneprotein, provides 250 kcal, 18 g protein) 3. If sores on tongue continue, recommend Mechanically Altered, Low Bacteria Diet 4. Encourage good po and fluid intake Monitor/Evaluation: 1. Anthropometrics, labs, po intake and diet tolerance, nutrition-focused physical findings, BM November 22, 2012, #D+7 Neutropen administered to increase WBC. The chart below shows WBC trending throughout his treatment, with the red line showing the date that conditioning began and the yellow line showing this day (11/22) when Neupogen was administered. The WBC increased significantly once administered and helped ease the mucositis pain over the following week.

(Normal count: 4.5-11 x 103 uL) Red line – conditioning treatment began Yellow line – pt started on Neupogen (11/22, #D+7) November 24, 2012, #D+9 Pt reported worsening mouth and throat pain (“dry, scratching”) along with difficulty swallowing due to mouth sores; noted to be grade II mucositis. He began swabbing with viscous lidocaine and using magic mouthwash. Diarrhea resolved at this point with the use of loperamide.

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November 25, 2012, #D+10 Pt had no BM x3 days and now presented with nausea and vomiting, triggered after he has eaten something. He was started on colace and senna. TPN noted to be a consideration if poor po intake continued. November 26, 2012, #D+11 Pt reported marked improvement of mouth and throat pain and less difficulty swallowing compared to previous day. He still reported very poor appetite and almost no po intake. There was no fever or other constitutional symptoms at this point. Mucositis began improving with return of WBC. +BM November 27, 2012, #D+12 Liver Consult - Liver was consulted secondary to cholestasis recognized in an increase in AST/ALT/bilirubin (as shown in the chart below). The etiology was likely hepatotoxicity from Fludarabine and Busulfan and indirect bilirubinemia from transfusions.

• At this point, pt denied any abdominal pain, but admitted to nausea, constipation, and diarrhea. Noted no history of ETOH, drug use, liver disease or family hx of liver disease. PT's WBC began uptrending on 11/26/12. Pt was being maintained on Prograf for immunosuppression.

November 28, 2012, #D+13 Pt reported feeling better however remained with poor appetite. He reported having improved stamina and one episode of vomiting. No fever or other constitutional symptoms were reported at this point.

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Nutrition Follow Up

Previous nutrition notes reviewed. During RD visit yesterday, pt reports feeling better with less mouth pain. Notes he will attempt to increase intake. Pt seen at bedside this am, reports feeling okay with increasing appetite, improved po intake x2 days (consumed bagel with cream cheese this am). Pt reports not liking the shake; will discontinue. Pt with no c/o N/V/D/C, however per MD note pt with emesis yesterday. Pt’s wife monitoring intake – reports intake is improving. BMT Day#: +13 Diet: Low Bacteria Supplements: none Labs: BUN 9, Alb 3.4, Abs neutrophils 3.55 (WNL) Meds: tacrolimus, magic mouthwash, cancidas, colace, senokot Anthropometrics Wt (11/28): 82.2 kg Wt (11/20): 82.8 kg Wt change: >1% BMI: 25 Nutrition Interventions:

1. Continue with low bacteria diet 2. Discontinue supplement 3. Dietary options reviewed for nausea/diarrhea – focused on soft, bland, low fiber foods 4. Encourage good po and fluid intake

Monitor/Evaluation:

1. Anthropometrics, labs, po intake and diet tolerance, nutrition-focused physical findings, BM November 29, 2012, #D+14 Neupogen discontinued Pt reported feeling better with his appetite improving. The day before he ate 3 small meals with no nausea or vomiting as his mouth/throat pain improved. He denied diarrhea but experienced occasional soft stools at this point (he was not taking an anti-motility agent). He was walking around with increased energy. November 30, 2012, #D+15 Pt reported feeling well and that mucositis pain in mouth and throat almost completely resolved. He is was tolerating a po diet well, +BM. No other complaints were offered. December 3, 2012 – DISCARGED Pt was discharged medically stable on low bacteria diet with no signs of GVHD. Low bacteria diet education was reinforced prior to discharge.

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CRITICAL COMMENTS MS was admitted in a relatively stable state nutritionally. He had not experienced any recent

changes in appetite or weight. From my initial assessment, I was able to gather that the patient

and his wife were well educated and understood the importance of nutrition in MS’s treatment.

During that assessment, I stated that my goals were to keep his weight stable by offering

supplements and food options when his appetite decreased or when he was unable to consume

adequate amounts of food. I also explained the Low Bacteria diet in detail, and the patient and

his wife asked appropriate questions.

After this initial assessment, I checked in with the patient weekly and monitored labs and weight

closely on days between visits. The interdisciplinary aspect of MS’s care team was extremely

helpful in monitoring this patient, as it was clear from their notes when and why certain labs and

medications changed. In addition, nutrition and intake were always noted. As expected, MS’s

intake dropped significantly as he began feeling the effects of the conditioning treatment. Oral

nutrition supplements were offered to increase protein and calorie intake; however, the patient

was not amenable to these shakes throughout his stay. During his period with mucositis, MS was

not eating anything which was a cause of concern and prompted the MD to suggest TPN if his

intake remained low. However, MS bounced back around #D+13 after the mucositis resolved

and his WBCs increased. Nutrition support was never necessary.

When looking back on the nutritional interventions, it would have been better if MS had not

experienced a period without intake. I understand that this is often unavoidable especially

during times of nausea and mucositis pain, but I was at a loss when he first refused the

supplemental shake due to a dislike of rice/soy milk (regular milk was not allowed due to his

period of diarrhea). I believe it may have been that he was not familiar with those products and

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therefore did not want to consume something foreign, especially during periods of nausea. If I

were to do anything over, I would have explained the importance of not consuming dairy during

his stay and the potential need for a non-dairy nutritional supplement during my initial

assessment and education. I would have possibly had him try a shake before feeling sick so he

could determine better whether he truly felt adverse to the taste or if it was the idea of rice/soy

milk, as he was unfamiliar with them prior to his admission. More generally, I learned that in the

future when working with this population, I should explain what to expect in terms of dietary

changes beyond the neutropenic diet based on this experience and the knowledge I gained from

writing this paper. This is a small change, but I believe it could make a big difference.

I would like to note that I believe the continuous monitoring, emphasis on the importance of

intake for success, and the formation of a trusting relationship with the patient helped contribute

to his nutritional success. MS was discharged only 3% lighter than when he was admitted, and

he left with the understanding of the importance of nutrition for his continued care.

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PATIENT UPDATE SCT patients are required to visit an outpatient clinic weekly for a period of time post-discharge,

therefore MS has been monitored closely since December 3rd when he left Mount Sinai. While

his stay at the hospital was relatively unremarkable in terms of complications, his status post-

discharge has declined slightly. As of the latest note on January 24th (#D+70), MS currently has

skin GVHD grade II-III and began taking Prednisone to help ease the symptoms. He was also

noted to have increased liver function tests (see the chart below for his bilirubin trend post-

discharge; the yellow shows stage I liver GVHD according to the criteria below) and diarrhea 1-

3x/day (volume not available).

Staging of Acute GVHD Skin Liver GI Tract Stage 1: <25% rash Stage 2: 25-50% rash Stage 3: generalized erythroderma Stage 4: bullae (blisters)

Stage 1: bili 2-3 mg/dL Stage 2: bili 3.1-6 mg/dL Stage 3: bili 6.1-15 mg/dL Stage 4: bili >15 mg/dL

Stage 1: diarrhea > 500 mL/day Stage 2: diarrhea > 1000 mL/day Stage 3: diarrhea > 1500 mL/day Stage 4: ileus, bleeding

Since each of symptoms is a sign of increasing GVHD, the doctor increased his

immunosuppressive regimen to include CellCept along with the Prograf and Prednisone. Per the

MD’s notes in the outpatient clinic, MS continues with a good appetite, no weight loss, and is

walking for exercise.

61

SUMMARY

Myelofibrosis treated with STC is a complicated process that involves a variety of interventions

and treatments that affect a patient’s nutritional status. When developing a nutritional plan in the

SCT population, it can be difficult to weigh the pros and cons of the many nutritional

interventions as a patient’s status can change daily. It is important to understand and follow the

evidenced-based research set for this population – especially when considering nutritional

support – in order to best serve the patient.

62

MEDICATION BIBLIOGRAPHY LIST OF PATIENT'S MEDICATIONS

Drug Class Medication Name Indications Diet/Nutritional Side Effects

Monitor

Antibiotic/Antiviral therapy

Acyclovir To treat/prevent bacteria infections during immunosuppression

Ensure adequate fluid intake; may lead to N/V/D/C, abd pain

Monitor renal function, may increase BUN, Cr, AST, ALT

Bronchodilator Albuterol (Proventil)

Allows pts to breathe more easily; also indicated to treat hyperkalemia

Sore dry throat Monitor K+, Glu, Chol

Antimalarial drug, Antiprotozoal agent

Atovaquone (Mepron)

Treat/prevent pneumonia caused by a fungal infection called of Pneumocystis carinii pneumonia (PCP)

- -

Antibiotic Bacitracin Polymyxin (Polysporin)

Wound healing - -

Antineoplastic Busulfan (Busulfex) Chemotherapy; treats blood cancers

N/V/D/C, hair loss, mouth sores, appetite/weight loss, headache, dry mouth, insomnia, anxiety, dizziness, chest pain, joint pain, itchiness, dry skin, darkened skin

Monitor CBC, weight, neutrophils

Corticosteroid Dexamethasone (Decadron)

Anti-inflammatory and immunosuppressant; used in cancer treatment to counteract chemo side effects

May lead to esophagitis, N/V, dyspepsia, peptic ulcer, bloating, GI bleeding/perforation Ca wasting with long term use - may lead to fractures/muscle wasting Steroid-induced diabetes May increase weight/appetite Negative N balance due to pro catabolism

Monitor electrolytes, adrenal function, glucose, BP, weight, bone density

Antihistamine Diphenhydramine (Benadryl)

Treats allergic reactions

- -

Laxative Docusate sodium (Colace)

Stool softener, for constipation

May cause bitter taste, nausea, diarrhea, cramps

Monitor electrolytes, I+O's

Anticoagulant Enoxaparin sodium (Lovenox)

Used to prevent and treat deep vein thrombosis or pulmonary embolism

- Monitor renal function, CBC, platelet count

Catecholamine Epinephrine Treats severe allergic reactions

63

Histamine H2-receptor antagonist

Famotidine (Pepcid)

Treats ulcers, gastroesophageal reflux disease (GERD), and conditions that cause the stomach to produce too much stomach acid

Do not take with Fe, Mg, antacids; may decrease Fe and Vit B12 abs; may cause N/V/D/C

Monitor hepatic func, Vit B12 with long term use

Colony-stimulating factor

Filgrastim (Neupogen)

Treats neutropenia during/after cancer treatment by increasing the production and activity of neutrophils (WBCs)

May cause bone pain, splenomegaly, nose bleed, fever

Monitor neutrophils, white blood cells

Antineoplastic Fludarabine (Fludara)

Chemotherapy; treats blood cancers; interfers with DNA synthesis

May cause stomatitis, dysphagia, N/V/D/C, hair loss, mouth sores, appetite/weight loss, headache, dry mouth, insomnia, anxiety, dizziness, chest pain, joint pain, itchiness, dry skin, darkened skin

Monitor CBC, weight, neutrophils

Hormone Glucagon Treats severe low blood sugar

Mouthwash Grade 0 mouthwash Prevents/treats chemotherapy-induced oral mucositis

- -

Corticosteroid Hydrocortisone Anti-inflammatory May lead to esophagitis, N/V, dyspepsia, peptic ulcer, bloating, GI bleeding/perforation Ca wasting with long term use - may lead to fractures/muscle wasting Steroid-induced diabetes May increase weight/appetite Negative N balance due to pro catabolism

Monitor electrolytes, adrenal function, glucose, BP, weight, bone density

Opioid Hydromorphone (Dilaudid)

Treats moderate to severe pain

Avoid grapefruit; may lead to dry mouth, dyspepsia, gastritis, N/V, diarrhea, constipation

Monitor liver enzymes, sodium

Antineoplastic Hydroxyurea (HU) Longterm use chemotherapy

Increase fluid intake; may lead to anorexia, stomatitis, N/V/D/C

Monitor baseline and periodic CBC with diff and platelets; hepatic, renal function

Anti-epileptic Levetiracetam (Keppra)

Used to treat seizures May lead to anorexia; do not take with renal dysfunction; may decrease RBC, Hb, HCT, WBC,

Monitor baseline CBC, renal function

64

neutrophils, platelets

Benzodiazepine, Anxiolytic, Antiemetic

Lorazepam (Ativan) Treats anxiety, anxiety with depression, and insomnia; also works to prevent/treat anxiety and the symptoms of anticipatory nausea and vomiting associated with chemotherapy

Caution when taking with grapefruit, chamomile, cafeeine; may cause anorexia, decreased wt, increased appetite; caution with hepatic/renal function

Monitor CBC with diff, hepatic and renal function

Mouthwash Magic Mouthwash Prevents/treats chemotherapy-induced oral mucositis

- -

Mineral supplement Magnesium chloride

Treats hypomagnesaemia

Take fiber, Fe, Fol separately by at least 2 hrs; may cause a chalky taste, N/V/D/C

Monitor Mg

Antineoplastic Methotrexate Treats several kinds of cancer, including cancer of the blood, bone, lung, breast, head, or neck; suppresses the immune system to help prevent transplant rejection

Encourage fluid intake; may decrease folate abs; may cause stomatitis, gingivitis, altered taste, N/V, diarrhea

Monitor baseline and periodic CBC with diff and platelets; hepatic, renal function, alb

Corticosteroid Methylprednisolone Anti-inflammatory May lead to esophagitis, N/V, dyspepsia, peptic ulcer, bloating, GI bleeding/perforation Ca wasting with long term use - may lead to fractures/muscle wasting Steroid-induced diabetes May increase weight/appetite Negative N balance due to pro catabolism

Monitor electrolytes, adrenal function, glucose, BP, weight, bone density

Narcotic Morphine Treats moderate to severe pain

Antifungal (oral treatment)

Nystatin (Mycostatin)

Treats fungal infections

May cause GI distress, N/V, stomach pain, diarrhea

-

Antiemetic Ondansetron (Zofran)

Prevents nausea and vomiting caused by cancer treatments

May cause dry mouth, abd pain, constipation, diarrhea

Monitor hepatic function

Opioid Oxycodone (Roxicodone)

Treats moderate to severe pain

Avoid grapefruit; may lead to dry mouth, dyspepsia, gastritis, N/V, diarrhea, constipation

Monitor liver enzymes, sodium

Mineral supplement Potassium chloride Treats hypokalemia; may cause N/V, abd pain, diarrhea

May cause GI distress, N/V/, abd pain, diarrhea, flatulence; caution with renal dysfunction, dysphagia; do not take

Monitor K+

65

with ESRD or GI ulcer

Corticosteroid Prednisone Treats inflammation and used to decrease some symptoms of cancer including mucositis, GVHD

May lead to esophagitis, N/V, dyspepsia, peptic ulcer, bloating, GI bleeding/perforation Ca wasting with long term use - may lead to fractures/muscle wasting Steroid-induced diabetes May increase weight/appetite Negative N balance due to pro catabolism

Monitor electrolytes, adrenal function, glucose, BP, weight, bone density

Antiemetic Prochlorperazine (Compazine)

Treats severe nausea and vomiting

May cause dry mouth, abd pain, constipation, diarrhea

Monitor hepatic function

Laxative Sennosides Treats constipation May cause electrolyte imbalances, N/V, cramps; need to consume adequate fluids

Monitor electrolytes, I+O's

Immunosuppressant Tacrolimus (Prograf)

An immunosuppressant -used after allo transplants to suppress the patient's immune system so to lower the risk of organ rejection; helps treat/prevent GVHD

May lead to anorexia, increased appetite, decreased Fe; may cause oral candidiasis, stomatitis, dysphagia, dyspepsia, N/V/D/C, gastritis, hemorrhage, GI perforation, abd pain, flatulence, HTN, hyperglycemia, hyperkalemia, hypomagnesemia, nephrotoxicity, neurotoxicity

Monitor baseline and periodic - BP, electrolytes, Mg, K+, renal function, hepatic function, CBC with diff, platelets, drug level

Bile acid Ursodiol Dissolves gallstones and treats primary biliary cirrhosis

May cause N/V, stomach pain

Monitor liver enzymes

Antibiotic/Antifungal therapy

Voriconazole To treat/prevent fungal infections during immunosuppression; treats mucositis, esophagitis

Take 1 hr before/after food; avoid SJW; may lead to dry mouth, N/V, abd pain, diarrhea; correct hypokalemia, hypocalcemia or hypomagnesemia prior to use. Do not take with hepatic dysfunction or renal dysfunction.

Monitor vision, hepatic, renal function, electrolytes

66

MEDICATION BIBLIOGRAPHY MEDICATIONS TO EASE TREATMENT SIDE EFFECTS34

Drug Brand Name Use Mechanism of action

Chlorpromazine Hydrochloride

Chlor-Trimeton®

Treatment of nausea and vomiting; psychoses; Tourette’s syndrome; mania; intractable hiccups (adults); behavioral problems (children)

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones

Dexamethasone Decadron® Systemically and locally for chronic inflammation, allergic, hematologic, neoplastic, and autoimmune diseases; may be used in management of cerebral edema, septic shock, and as a diagnostic agent

Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability; suppresses normal immune response

Diphenhydramine HJydrochloride

Benadryl® Allergy

Symptomatiac relief of allergic symptoms caused by histamine release that include nasal allergies and allergic dermatosis; milk nighttime sedation, prevention of motion sickness, as an antitussive; treatment of metoclopramide-or phenothiazine-inducced dystonic reactions

Competes with histamine for H1 receptor sites on effector cells in the GI tract, blood vessels, and respiratory tract

Dronabinol Marinol® Treatment of nausea and vomiting secondary to cancer chemotherapy in patients who have not responded to conventional antiemetics; treatment of anorexia associated with weight loss in AIDS patients

Dronabinol is the principal psychoactive substance found in Cannabis sativa (marijuana); its mechanism of action as an antiemetic is not well defined, it probably inhibits the vomiting center in the medulla oblongata; has complex effects on CNS including central sympathomimetic activity

Droperidol Inapsine® Tranquilizer and antiemetic in surgical and diagnostic procedures; antiemetic for caner chemotherapy; preoperative medication

Alters the action of dopamine in the CNS at subcortical levels to produce sedation and a dissociative state; also possesses alpha-adrenergic blockade effects

Granisetron Kytril® Prophylaxis and treatment of chemotherapy and radiation-related nausea and emesis; prophylaxis and treatment of postoperative nausea and vomiting

Selective 5-HT3 receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone

Hydroxyzine Vistaril® Treatment of anxiety; preoperative sedative; antipruritic; antiemetic

Competes with histamine for H1 recceptor sites on effector cells in the GI tract, blood vessels, and respiratory tract

67

Lorazepam Ativan®; Lorazepam Intensol®

Management of anxiety; status epilepticus; preoperative sedation and amnesia

Depresses all levels of the CNS, including the limbic and reticular formation, by binding to the benzodiazepine site on the gamma-aminobutyric acid (GABA) receptor complex and modulating GABA, which is a major inhibitory neurotransmitter in the brain

Metoclopramide Reglan® Gastroesophageal reflux; prevention of nausea associated with chemotherapy; facilities intubation of the small intestine and symptomatic treatment of diabetic gastric stasis

Potent dopamine receptor antagonist; blocks dopamine receptors in chemoreceptor trigger zone of the CNS, preventing emesis; accelerates gastric emptying and intestinal transit time without stimulating gastric, biliary, or pancreatic secretions

Odansetron Zofran® ODT; Zofran®

Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy and prevention of postoperative and radiation-induced nausea and vomiting

Selective 5-HT3 receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone

Prochlorperazine

ComproTM Management of nausea and vomiting; acute and chronic psychosis

Blocks postsynaptic mesolimbic dopminergic receptors in the brain, including the medullary chemoreceptor trigger zone; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones

Promethazine Hydrochloride

Phenergan®; PrometheganTM

Antiemetic; symptomatic treatment of various allergic conditions and motion sickness; sedative

Blocks postsynaptic mesolimbic dopaminergic receptors in the brain; exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; competes with histamine for the H1-receptor

Trimethobenzamide Hydrochloride

Tigan® Control of nausea and vomiting (especially for long-term antiemetic therapy)

Acts centrally to inhibit stimulation of the medullary chemoreceptor trigger zone

68

MEDICATION BIBLIOGRAPHY IMMUNOSUPPRESSIVE MEDICATIONS AND TREATMENTS USED IN GRAFT-VS-HOST DISEASE 23

Medicine or Treatment

Mechanism of Action Nutrition-Related Side Effects

Corticosteroids (systemic, topical, and mouthwash)

Anti-inflammatory response at arterial site inhibits IL-1 and decreases IL-2, which suppresses lymphocyte proliferation and decreases circulating lymphocytes

Fluid and sodium retention, hyperglycemia, hypertriglyceridemia, hypercholesterolemia, increased appetite, weight gain, muscle wasting, bone demineralization

Cyclosporine Inhibits response of cytotoxic T cells to IL-2 and prevents T helper lymphocytes from producing IL-2

HTN, hyperglycemia, hyperkalemia, hypomagnesemia, hyperlipidemia, gingival hyperplasia, nephrotoxic, neurotoxic

Tacrolimus Inhibits proliferation of cytotoxic T cells and synthesis of IL-2

HTN, hyperglycemia, hyperkalemia, N/V/D, hypomagnesemia, nephrotoxicity, neurotoxicity

Methotrexate Antimetabolite, antineoplastic, immunosuppressant

Anorexia, N/V/D, stomatitis, mucositis, elevated liver function tests, renal failure, cirrhosis

Mycophenolate mofetil

Decreases lymphocyte activation and replication by suppressing enzymes in the purine salvage pathway, creating a purine deficiency and thus inhibiting T and B cell proliferation; suppresses antibody formation

N/V/D/C, GI bleeding, peripheral edema, sepsis

Sirolimus Inhibits T and B cell proliferation while not affecting IL-2 production

Hypercholesterolemia, hypertriglyceridemia, HTN, peripheral edema

Thalidomide Anti-inflammatory and immunosuppressive properties

Neuropathy, C, neutropenia

Antithymocyte globulin (ATG)

Decreases circulating lymphocytes Abdominal pain, N/V/D, hyperkalemia, HTN, peripheral edema, sepsis

Etanercept TNF-# antagonist or binder Abdominal pain, V, rhinitis

Ursodeoxycholic acid Replaces native human bile acids, reduces class I HLA expression on hepatocytes

N/V/D, abdominal pain

Daclizumab Humanized anti-IL-2 receptor antibody V, edema, HTN, hypotension, fever, dyspnea, infection

Azathioprine Inhibits RNA and DNA synthesis to prevent cytotoxic T and B cell proliferation and antibody production

GI hypersensitivity, hepatotoxicity, megaloblastic anemia, pancreatitis, infection, bone marrow suppression

Hydroxychloroquine Interferes with antigen processing and presentation, proliferation, TNF-# production, and cytotoxicity, synergistic with cyclosporine and tacrolimus in vitro

N/V/D

Infliximab Humanized chimeric antibody against TNF-#, IgG monoclonal antibody

Abdominal pain, N/V, worsening CHF

69

Psoralen and PUVA Interferes with antigen presentation and inflammatory cytokine production by Langerhan's cells, increases IL-10 production by keratinocytes

Increase in skin cancer, phototoxicity, N, hepatotoxicity

Extracorporeal photopheresis

Induces apoptosis in alloreactive T cells, normalization of CD4/CD8 ratios by decreasing CD8 cells, increases natural killer cells, decreases dendritic cells, photoinactivation of antigen presenting cells and T lymphocytes

GI upset, hypocalcemia (if citrate anticoagulant used)

N, nausea; V, vomiting; D, diarrhea, C, constipation; HTN, hypertension; Abd, abdominal; CHF, congestive heart failure; GI, gastrointestinal; TNF, tumor necrosis factor; IL, interleukin; HLA, human leukocyte antigen; IgG, immunoglobulin G.

70

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http://www.cancer.gov/cancertopics/pdq/treatment/myeloproliferative/Patient/page1. Accessed December 10, 2012.

2. Myelofibrosis Facts. The Leukemia & Lymphoma Society Web Site. www.lls.org/content/.../mpd/pdf/idiopathicmyelofibrosis.pdf. Accessed December 10, 2012.

3. Tefferi A. Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. Am J Hematol. 2011 Dec;86(12):1017-26. doi: 10.1002/ajh.22210.

4. Reilly JT, McMullin MF, Beer PA, Butt N, Conneally E, Duncombe A. Guideline for the diagnosis and management of myelofibrosis. Br J Haematol. 2012 Aug;158(4):453-71. doi: 10.1111/j.1365-2141.2012.09179.x. Epub 2012 Jun 1.

5. Gregory SA, Mesa RA, Hoffman R, Shammo JM. Clinical and laboratory features of myelofibrosis and limitations of current therapies. Clin Adv Hematol Oncol. 2011 Sep;9(9 Suppl 22):1-16.

6. Randhawa J, Ostojic A, Vrhovac R, Atallah E, Verstovsek S. Splenomegaly in myelofibrosis--new options for therapy and the therapeutic potential of Janus kinase 2 inhibitors. J Hematol Oncol. 2012 Aug 1;5:43. doi: 10.1186/1756-8722-5-43.

7. Tefferi A, Vardiman JW: Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008, 22:14–22.

8. Beer PA, Campbell PJ, Green AR. Comparison of different criteria for the diagnosis of primary myelofibrosis reveals limited clinical utility for measurements of serum lactate dehydrogenase. Haematologica. 2010 Nov;95(11):1960-3. doi: 10.3324/haematol.2010.026708. Epub 2010 Jun 9.

9. Tefferi A, Elliott MA, Pardanani A. Atypical myeloproliferative disorders: diagnosis and management. Mayo Clin Proc. 2006 Apr;81(4):553-63.

10. Gupta V, Foltz L, Sirhan S, Busque L, Turner AR. Emerging therapeutic options for myelofibrosis: a Canadian perspective. Am J Blood Res. 2012;2(3):170-86. Epub 2012 Sep 23.

11. Use of Hydroxyurea in Patients with Sickle Cell Disease. Harvard.edu Website. http://sickle.bwh.harvard.edu/hyguid.html. Accessed December 20, 2012.

12. Types of Chemotherapy Agents and Regimens. Chemoth.com Website. http://chemoth.com/types/alkylating. Accessed December 10, 2012.

13. Interferons. National Multiple Sclerosis Society Web Site. http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/treatments/medications/interferons/index.aspx. Accessed December 20, 2012.

14. Ianotto JC, Kiladjian JJ, Demory JL, Roy L, Boyer F, Rey J, Dupriez B, Berthou C, Abgrall JF. PEG-IFN-alpha-2a therapy in patients with myelofibrosis: a study of the French Groupe d'Etudes des Myelofibroses (GEM) and France Intergroupe des syndromes Myéloprolifératifs (FIM). British Journal of Haematology. 2009 Jul;146(2):223-5. Epub 2009 May 26.

15. Charuhas PM, Lipkin A, Lenssen P, McMillen K. Hematopoietic Stem Cell Transplantation. The A.S.P.E.N. Nutrition Support Practice Manual, 2nd Edition. American Society for Parenteral and Enteral Nutrition. 2005.

16. Parrish CR, Nutrition Support of Blood or Marrow Transplant Recipients: How Much Do We Really Know? Nutrition Issues in Gastroenterology, Series #26.

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17. Blood and Marrow Stem Cell Transplantation. The Leukemia & Lymphoma Society Website. http://www.lls.org/bloodmarrowstemcelltransplantation-1. Accessed December 15 2012.

18. Gupta V, Hari P, Hoffman R. Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors. Blood. 2012 Aug 16;120(7):1367-79. doi: 10.1182/blood-2012-05-399048. Epub 2012 Jun 14.

19. Nelms, M., Sucher, K., Lacey, K., Roth, S. L. (2011). Nutrition Therapy and Pathophysiology, 2e. Belmont, Ca: Wadsworth, Cengage Learning.

20. Finkel, Yigael M.D., Ph.D.; Baker, , Robert D. Jr. M.D., Ph.D.; Rosenthal, Philip M.D.; Sherman, Philip M. M.D., F.R.C.P.C.; Sondheimer, Judith M. M.D. A Critical Perspective on Trophic Feeding. Journal of Pediatric Gastroenterology & Nutrition: March 2004 - Volume 38 - Issue 3 - pp 237-238

21. Kumar S, DeLeve LD, Kamath PS, Tefferi A. Hepatic veno-occlusive disease (sinusoidal obstruction syndrome) after hematopoietic stem cell transplantation. Mayo Clin Proc. 2003 May;78(5):589-98.

22. Muscaritoli M, Grieco G, Capria S, Iori AP, Rossi Fanelli F. Nutritional and metabolic support in patients undergoing bone marrow transplantation. Am J Clin Nutr. 2002 Feb;75(2):183-90. Review.

23. Roberts S, Thompson J. Graft-vs-host disease: nutrition therapy in a challenging condition. Nutr Clin Pract. 2005 Aug;20(4):440-50.

24. Normen L, Bosaeus I, Ekman T. Nutritional therapy during bone marrow transplantation. An overview. Scandinavian Journal of Nutrition; Vol 40: 156-160, 1996.

25. August DA, Huhmann MB; American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Board of Directors. A.S.P.E.N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J Parenter Enteral Nutr. 2009 Sep-Oct;33(5):472-500.

26. Hoffman R, Benz EJ, Silberstein L, Heslop H, Weitz J, Anastasi J. Hematology: Basic Principles and Practice, 6th ed. Philadelphia, PA: Saunders; 2013.

27. Lipkin AC, Lenseen P, Dickson BJ. Nutrition Issues in Hematopoietic Stem Cell Transplantation: State of the Art. Nutrition in Clinical Practice 2005 20:423.

28. Moody K, Charlson ME, Finlay J. The neutropenic diet: what's the evidence? J Pediatr Hematol Oncol. 2002;24(9):717-21.

29. Neutropenic Diet . Leukemia and Lymphoma Society Web Site. http://www.lls.org/diseaseinformation/managingyourcancer/treatmentnextsteps/foodnutrition/neutropenicdiet/. Accessed January 10, 2013.

30. Platelet Definition. Gene Wiki Web Site. http://genewikiplus.org/wiki/Platelet. Accessed January 14, 2013.

31. Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants). American Cancer Society Web Site. http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/bonemarrowandperipheralbloodstemcelltransplant/bone-marrow-and-peripheral-blood-stem-cell-transplant-toc. Accessed January 14, 2013.

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32. van der Meij BS, de Graaf P, Wierdsma NJ, Langius JA, Janssen JJ, van Leeuwen PA, Visser OJ. Nutritional support in patients with GVHD of the digestive tract: state of the art. Bone Marrow Transplant. 2012 Jul 9. doi: 10.1038/bmt.2012.124.

33. Graft versus Host Disease. PubMed Health, A.D.A.M. Health Solutions Web Site. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002286/. Accessed January 2, 2013.

34. American Dietetic Association. Nutrition Care Manual®. http://nutritioncaremanual.org. Accessed January 15, 2013.

Dietary advice for

patients with neutropenia

Revised January 2012

This publication has been produced and prepared by the London

Haem

atology Dietitians G

roup for patients who m

ay be at risk of food borne infection due to high dose chem

otherapy and/or bone marrow

or stem cell transplants.

Leukaemia &

Lymphom

a Research are acting as publishers but responsibility

for content and the copyright in the content remain w

ith the London H

aematology D

ietitians Group. T

he contents of this booklet are believed to be correct at the date of publication. H

owever, it is not exhaustive, and none

of the persons or organisations concerned with the supply of inform

ation or production of this booklet accepts any liability for any error, om

ission or m

isstatement contained therein. T

his booklet is intended for information only.

The inform

ation contained within this booklet is based, w

here possible, on available evidence and agreed best practice. It is not a substitute for a proper m

edical diagnosis or dietary advice given by a Registered D

ietitian (RD

). If patients have any queries please refer back to the person w

ho gave you this

booklet.

At all tim

es patients should rely on the advice of their specialist w

ho is the only person with full inform

ation about their diagnosis and m

edical history.

For further information please contact the patient inform

ation team

on 020 7504 2200.

The inform

ation in this booklet is correct at the time of going to print.

Leukaemia &

Lymphom

a Research,

39-40 Eagle Street, London WC

1R 4T

HT: 020 7504 2200 E: info@

beatingbloodcancers.org.ukW

: beatingbloodcancers.org.uk

Series compiled by K

en Cam

pbell MSc, revised January 2012.

© A

ll rights reserved. No part of this publication m

ay be reproduced or transmitted,

in any form or by any m

eans, electronic or mechanical, including photocopying,

recording or any information storage and retrieval system

, without perm

ission in w

riting from the London H

aematology D

ietitians Group or Leukaem

ia & Lym

phoma

Research.

11

Following chem

otherapy there is a risk of infection from bacteria

or fungus in foods. This is for tw

o reasons: 1) The w

hite blood cells

(neutrophils) that would usually fight food poisoning bacteria are

at a low level. T

his is referred to as neutropenia. 2) The gut lining acts

as a barrier between bacteria and the bloodstream

. Chem

otherapy and

radiotherapy damage the gut lining m

aking it easier for any bacteria

to cross this barrier.

During neutropenia, the follow

ing guidelines will help to reduce the risk

of food poisoning whilst still allow

ing as varied a diet as possible. There

is no single agreed definition of neutropenia or severe neutropenia;

the levels quoted below are very w

idely used but if a doctor uses

different levels, patients should be guided by those. The type of advice

to be followed is dependent on the num

ber of white blood cells in the

bloodstream: this is know

n as the neutrophil count.

This booklet provides general advice on safe food handling and storage

for all patients at risk of neutropenia. This advice should be follow

ed

at all times by patients, their fam

ilies and friends. It also lists some foods

that patients with neutropenia should avoid –

for those with a neutrophil

count of 0.5-2.0 x 109/litre and those w

ith a neutrophil count below

0.5 x 109/litre. T

he booklet also offers suggestions for suitable snacks for

patients with neutropenia.

Patients should check their neutrophil count with the doctor or nursing

staff and follow the advice both in hospital and at hom

e. Please note

that the level of restriction required may vary dependent upon clinical

condition and appropriate advice will be given. A

fter a bone marrow

or

stem cell transplant, or w

hen on imm

unosuppressive medication, it m

ay be

necessary to continue following these guidelines after the neutrophil count

has recovered. This is because the im

mune system

is weaker, increasing risk

of infections. If any questions arise regarding this diet or eating in general,

the doctor or nurse specialist can refer patients to a dietitian for specialist

assessment and advice.

INT

ROD

UC

TIO

N

2

FOO

D SA

FETY

General advice

Shopping

Avoid buying food

w

ith damaged or broken packaging

from

fridges or freezers that are overloaded as the food may not

be cold enough

Buy chilled and frozen foods last and get them

home as quickly as

possible. If it is not possible to get food home im

mediately, an insulated

container or cool bag can help to keep food at the correct temperature

Alw

ays check best before or use by dates on packaging

Avoid shops w

here raw and cooked m

eats are stored in the same fridge

or in a deli counter without a separating w

all. Where possible buy

pre-packed deli items

Storage

The fridge should be kept betw

een 0°C

and 5°C

The freezer should be kept below

-18°C

. Alw

ays ensure that food is still

frozen solid when it is rem

oved from the freezer

Store cooked food at the top of the fridge

Raw

or defrosting meat or fish should be stored at the bottom

of the fridge in a covered container to prevent dripping or leaking

into the fridge

Do not overload the fridge or freezer as this w

ill increase

the temperature

Eggs should be stored in the fridge

Use and store food as per m

anufacturer's instructions and within

best before or use by dates

Never refreeze thaw

ed food

13

Food preparation

Hands should alw

ays be washed w

ith warm

water and soap before

preparing food

Hands m

ust be washed after going to the toilet, sneezing and after

touching pets, hair, dirty washing, rubbish, ready-m

ade or raw food

Use a separate tow

el or use kitchen paper to dry hands, do not use a

tea towel.

Cover any cuts and grazes w

ith a waterproof plaster

Keep pets aw

ay from w

ork surfaces, food and your dishes

Ensure any cloths or sponges are regularly bleached, disinfected or changed

Avoid cross-contam

ination of food by changing or washing chopping

boards and utensils between raw

and cooked food

Disinfect w

ork surfaces regularly

Wash can tops before opening them

Wash fruit and vegetables before eating

Cooking

Thaw

meat and poultry in a fridge and not at room

temperature

as bacteria grow quickly at room

temperature

Cook all food thoroughly and ensure it is piping hot all the w

ay through

Cook m

eat until the juices are clear

Pre-heat the oven to ensure food is cooked at the recom

mended tem

perature

Alw

ays follow m

anufacturer's guidelines and do not shorten

cooking times

Do not reheat cooked food

4

Microw

ave cookers can be used for defrosting and for heating prepared

foods according to manufacturer’s instructions

Do not put hot food in the fridge, as this w

ill increase the temperature

of all food in the fridge making it unsafe to eat

Cool food at room

temperature w

ithin an hour after cooking and then

chill or freeze

Eating out

Ensure food is piping hot when served and cooked all the w

ay through

Choose freshly prepared foods from

reputable outlets. Avoid salad bars,

street vendors, market stalls and ice cream

vans

5

Specific food safety advice for a neutrophil count of 0.5-2.0 x 10

9/litreT

his list provides all the relevant examples of high risk foods that should

be avoided and suitable alternatives.

Avoid

Alternatives

Soft ripened cheese e.g. Brie,

Cam

embert, goat’s cheese,

paneer and labnah

Processed cheese e.g. Dairylea, K

raft, Philadelphia, m

esh and halloumi

Blue veined cheese e.g. D

anish blue and Stilton

Vacuum-packed pasteurised and hard

cheese e.g. cheddar and Edam

Raw

or lightly cooked shellfishW

ell cooked shellfish e.g. prawn

curry

Raw

/undercooked meat, poultry

or fish e.g. meat w

hich is still pink and sushi; sm

oked items e.g. salm

on or Parm

a ham, salam

i, caviar and oysters

Well cooked m

eat, poultry and fish; vacuum

-packed cold meats such as

turkey and ham; tinned m

eat and fish

Raw

eggs or undercooked eggs e.g. hom

emade m

ayonnaise, hom

emade ice cream

, mousse,

egg-nog, meringue and

hollandaise sauce

Hard boiled eggs; shop bought

mayonnaise, ice cream

and other products m

ade with pasteurised egg

Probiotics, live or bio products e.g. live yoghurts, probioticcontaining supplem

ents and drinks

Pasteurised plain, fruit yoghurts e.g. thick and cream

y or Greek yoghurts

or yoghurt products e.g. lassi

PatéPasteurised paté and paste in tins or jars that do not need to be refrigerated

All unpasteurised dairy products

e.g. unpasteurised cheese such as parm

esan or milk sold on local farm

s

Any pasteurised m

ilk, soya milk,

Jersey milk, U

HT

milk and

cheese products

FOO

D SA

FETY

AD

VIC

E D

UR

ING

NEU

TRO

PENIA

6

Specific food safety advice for a neutrophil count below

0.5 x 109/litre

In addition to the advice on page five for food safety, it is recomm

ended

that you also follow the diet for severe neutropenia w

hen your neutrophil

count falls below 0.5 x 10

9/litre.

This m

eans that you will have a few

further restrictions to consider. Foods

to avoid as well as the recom

mended alternatives are listed below

.

Please check with your hospital for their policy regarding foods brought in

by visitors and supply of ice cream.

Avoid

Alternatives

Raw

unpeeled fruit or vegetables including salad item

s, stuffed vine leaves, fatoosh and taboulleh; raw

dried fruit, products containing these e.g. m

uesli, Bom

bay mix,

confectionary; damaged or over-ripe

fruit or vegetables; unpasteurised or freshly squeezed fruit or vegetable juice or sm

oothies

Good quality fruit and vegetables

that are well cooked or peeled; U

HT

or long-life fruit juices –

in cartons or jars; pasteurised sm

oothies; tinned fruit; cooked dried fruit e.g. in fruitcake, flapjacks or cereal bars

Uncooked herbs, spices and pepper

Cooked herbs, spices and pepper

Non-drinking w

ater, bottled mineral

or spring water, w

ater from w

ells, w

ater from coolers and

water fountains

Freshly run tap/filtered/sterilised/carbonated w

aterPlease check w

ith your hospital for guidance.

Unpasteurised or “farm

fresh” honey and honeycom

bPasteurised or heat-treated honey

Unnecessarily large packets of food

items from

pick and mix, universal

jars; deli counter foods e.g. olives, houm

us, shawirm

a and baklava

Ideally, packets should be for personal use only e.g. butter, sw

eets, pickles, sm

all packets of food, houmus

and baklava

17

FOO

D SU

GG

ESTIO

NS

If you have a poor appetite and are finding it difficult to manage your

meals w

hilst neutropenic, try some of these nourishing snacks:

Savoury C

heese and crackers

Cheese spread or baked beans on toast

Jacket potato

Tinned spaghetti

Fried rice with cooked m

eat added

Rice porridge w

ith cooked meat added

Sandwiches –

try adding salad cream or m

ayonnaise

Breakfast cereals (at any tim

e)

Toasted muffins

Meat dum

plings/buns

Processed cheese such as Dairylea triangles, K

raft cheese slices

or halloumi cheese

Roasted nuts, crisps and dips

Sweet

Chocolate or plain, sw

eet biscuits

Sweets and chocolates –

individual or bars

Thick and cream

y style yoghurts and fromage frais

Individual cold desserts and tinned puddings. Try adding cream

or custard

Buttered hot cross buns or sw

eet waffles w

ith syrup

Individually packaged baklava

8

Malt loaf or fruitcake

Tinned fruit and cream

/ice cream

Kheer m

ade with pasteurised m

ilk

Croissants

Peanut brittle

Liquids Soups –

condensed and creamed varieties

Milky drinks –

Ovaltine, cocoa, H

orlicks and hot chocolate

Milkshakes

Fizzy drinks, long-life fruit juice, squashes and cordials

Nutritional supplem

ents B

uild up, Com

plan or prescribed nutritional supplements such

as Fortisip, Ensure Plus, Resource Shake, C

linutren 1.5 or Fresubin

Energy drink

If you are advised by your dietitian or other healthcare professional to

take nutritional supplements these can be stored unopened at room

temperature. O

nce opened these drinks should be stored; unrefrigerated

for up to 4 hours; refrigerated for up to 24 hours.

19

NO

TES

DA

PN 01/12

Acute Prom

yelocytic Leukaem

ia (APL)

Adult A

cute Lym

phoblastic Leukaemia (A

LL)

Adult A

cute M

yeloid Leukaemia (A

ML)

Childhood A

cute Lym

phoblastic Leukaemia (A

LL)

Childhood A

cute M

yeloid Leukaemia (A

ML)

Chronic Lym

phocytic Leukaem

ia (CLL)

Chronic M

yeloid Leukaemia (C

ML)

Aplastic A

naemia (A

A)

The M

yelodysplastic Syndrom

es (MD

S)

The M

yeloproliferative N

eoplasms (M

PN)

Multiple M

yeloma (M

M)

Hodgkin Lym

phoma (H

L)

Non-H

odgkin Lymphom

a (NH

L)

Bone M

arrow and Stem

Cell

Transplantation (BM

T)

– for children and adults

Donating stem

cells –

what's involved?

Donor Lym

phocyte Infusion (DLI) –

w

hat’s involved?T

he Seven Steps – B

lood & bone

marrow

transplantationU

ndergoing high dose therapy and autologous stem

cell transplantC

hemotherapy

– w

hat do I need to know?

Clinical Trials

Com

plementary and

Alternative M

edicine (CA

M)

Dietary advice for patients

with neutropenia

Supportive careTreatm

ent decisionsW

atch and wait

Young adults with a blood cancer –

w

hat do I need to know?

Jack's Diary: an illustrated children's

book to help young patients understand and deal w

ith blood cancers, treatm

ent and life changesW

iggly's World: a colourful A

-Z

illustrated booklet, designed to take the anxiety out of treatm

ent for children and their parents

Leukaemia &

Lymphom

a Research, 39-40 Eagle Street, London W

C1R

4TH

T: 020 7504 2200

E: info@beatingbloodcancers.org.uk • W

: beatingbloodcancers.org.uk

Registered charity 216032 (England &

Wales) SC

037529 (Scotland)

The follow

ing patient information booklets are available free of charge from

Leukaem

ia & Lym

phoma R

esearch. You can download them

from our w

ebsite or request copies by phone.

Leaflets on a range of associated blood disorders are also available from

Leukaemia &

Lym

phoma R

esearch